@article{AertsEberleinHolmetal.2021,
  author    = {Aerts, An and Eberlein, Uta and Holm, S{\"o}ren and Hustinx, Roland and Konijnenberg, Mark and Strigari, Lidia and van Leeuwen, Fijs W. B. and Glatting, Gerhard and Lassmann, Michael},
  title     = {EANM position paper on the role of radiobiology in nuclear medicine},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {48},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {11},
  doi       = {10.1007/s00259-021-05345-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265595},
  pages     = {3365-3377},
  year      = {2021},
  abstract  = {With an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.},
  language  = {en}
}
@phdthesis{Andermann2007,
  author    = {Andermann, Paul},
  title     = {Evaluierung der Intra- und Interobserver-Variabilit{\"a}t bei der 2D-Ultraschall-Schilddr{\"u}senvolumetrie an einem Schilddr{\"u}senphantom - Vergleich zu 3D-Ultraschall-Referenzmessungen an gesunden Probanden},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-23434},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Mehrere Autoren haben schon die Intra- und Interobserver-Variabilit{\"a}t bei der Bestimmung des Schilddr{\"u}senvolumens und knotiger Herdbefunde mit Hilfe des zweidimensionalen (2D) Ultraschalls evaluiert. Dar{\"u}ber hinaus wurde {\"u}ber Interobserver-Korrelationen f{\"u}r Schilddr{\"u}senvolumenmessungen berichtet. Es gibt jedoch keine prospektive verblindete Studie, die die Intra- bzw. Interobserver-Variabilit{\"a}t bei der Volumenbestimmung der gesamten Schilddr{\"u}se an gesunden Probanden bzw. einzelner Knoten unterschiedlicher Echogenit{\"a}t an einem Phantom untersucht hat. Die Ergebnisse der Einzelstudien sollen hier vorgestellt und - soweit m{\"o}glich - miteinander verglichen werden. Im Rahmen einer quantitativen Studie mit dem hier pr{\"a}sentierten Schilddr{\"u}senphantom soll die Intra- und Interobserver-Variabilit{\"a}t bei der 2D-Ultraschallvolumetrie einzelner Knoten unterschiedlicher Gr{\"o}ße und Echogenit{\"a}t und der Schilddr{\"u}senlappen evaluiert werden. Da Schilddr{\"u}senknoten wegen des geringeren Volumens und ihrer oft unscharfen Randkontur schwieriger zu entdecken und auszumessen sind als die Gesamtschilddr{\"u}se, soll untersucht werden, welche Gr{\"o}ßenordnungen des Messfehlers auftreten und in welcher Relation sie zueinander stehen. Außerdem soll der methodenimmanente Fehler quantifiziert und detektierbare Volumen{\"a}nderungen erfassbar gemacht werden. Bisher war in der Schilddr{\"u}sensonographie kein geeignetes Phantom verf{\"u}gbar, das kommerziell erh{\"a}ltlich ist und mit dem qualitativ unterschiedliche intrathyreoidale Herdbefunde untersucht werden k{\"o}nnen. Die vorliegende Studie an gesunden Probanden hatte das prim{\"a}re Ziel, die Frage nach der Quantifizierbarkeit von Unsicherheitsfaktoren in der Schilddr{\"u}senvolumetrie durch den konventionellen 2D-Ultraschall im Vergleich zu 3D-Referenzvolumina bei gesunden Erwachsenen m{\"o}glichst exakt zu beantworten und die Untersucherabh{\"a}ngigkeit der Methode zu demonstrieren. Damit soll die Genauigkeit (Richtigkeit und Pr{\"a}zision) der sonographischen Schilddr{\"u}sendiagnostik mathematisch erfasst und eine bessere Bewertungsgrundlage f{\"u}r die Frage nach der Reproduzierbarkeit von Ultraschall-Volumenbestimmungen der Schilddr{\"u}se und ihrer pathologischen Ver{\"a}nderungen geschaffen werden. Hierf{\"u}r wurden m{\"o}glichst aussagekr{\"a}ftige statistische Parameter wie die Intra- und Interobserver-Variabilit{\"a}t, der systematische und zuf{\"a}llige Fehler, der reine Fehler der Messmethode, minimale, sicher detektierbare Volumen{\"a}nderungen und im Rahmen einer multivariaten Reliabilit{\"a}tsanalyse die Reliabilit{\"a}tskoeffizienten untersucht. Ein weiteres Ziel dieser Studie bestand darin, die Reliabilit{\"a}t der in der klinischen Routine benutzten Ellipsoidformel zur Berechnung des Schilddr{\"u}senvolumens zu {\"u}berpr{\"u}fen.},
  language  = {de}
}
@article{AngheloiuHaenscheidWenetal.2012,
  author    = {Angheloiu, George O. and H{\"a}nscheid, Heribert and Wen, Xiaoyan and Capponi, Vincent and Anderson, William D. and Kellum, John A.},
  title     = {Experimental first-pass method for testing and comparing sorbent polymers used in the clearance of iodine contrast materials},
  series = {Blood Purification},
  volume    = {34},
  journal   = {Blood Purification},
  number    = {1},
  issn      = {0253-5068},
  doi       = {10.1159/000339816},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199118},
  pages     = {34-39},
  year      = {2012},
  abstract  = {Background: Sorbents have been shown to adsorb iodinated radiocontrast media. Objective: In this study we describe a simple method to compare various sorbents in terms of capacity to adsorb radiocontrast media. Methods: Iodixanol solution was injected into columns filled with three types of sorbent at filtration velocities of increasing magnitude. Two variables of interest - contrast removal rate and matched iodine retention (MIR) - were calculated to measure the adsorption efficiency and the mass of contrast iodine adsorbed versus sorbent used, respectively. Results: The highest contrast removal and MIR for Porapak Q, CST 401 and Amberlite XAD4 were 41, 38 and 16\% (p = 0.22 and 0.0005 for comparisons between Porapak Q-CST 401 and CST 401-Amberlite XAD4) and 0.060, 0.055 and 0.024, respectively (p = 0.18 and 0.0008). Extrapolation to a clinical scenario may suggest that removal of 8 ml iodixanol could be achieved by masses of sorbents of 43, 47 and 107 g, respectively. Conclusion: In this study we set a benchmark for comparing the radiocontrast-adsorbing efficiency of polymer sorbents during first-pass experiments, using a readily available methodology.},
  language  = {en}
}
@article{AsterRomanosWalitzaetal.2022,
  author    = {Aster, Hans-Christoph and Romanos, Marcel and Walitza, Susanne and Gerlach, Manfred and M{\"u}hlberger, Andreas and Rizzo, Albert and Andreatta, Marta and Hasenauer, Natalie and Hartrampf, Philipp E. and Nerlich, Kai and Reiners, Christoph and Lorenz, Reinhard and Buck, Andreas K. and Deserno, Lorenz},
  title     = {Responsivity of the striatal dopamine system to methylphenidate — A within-subject I-123-β-CIT-SPECT study in male children and adolescents with attention-deficit/hyperactivity disorder},
  series = {Frontiers in Psychiatry},
  volume    = {13},
  journal   = {Frontiers in Psychiatry},
  issn      = {1664-0640},
  doi       = {10.3389/fpsyt.2022.804730},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270862},
  year      = {2022},
  abstract  = {Background: Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight on how the effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning. Methods Thirteen adolescent male patients (9-16 years) with a diagnosis of ADHD according to the DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-β-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in an on- and off-MPH status balanced for order across participants. A virtual reality continuous performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH. Results On-MPH status was associated with a highly significant change (-29.9\%) of striatal DAT BP as compared to off-MPH (t = -4.12, p = 0.002). A more pronounced change in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r = 0.68, p = 0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings (Pearson r = 0.56, p = 0.04). Conclusion Our findings corroborate previous reports from mainly adult samples that MPH changes striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity.},
  language  = {en}
}
@article{BaurSchedelbeckPulzeretal.2015,
  author    = {Baur, Johannes and Schedelbeck, Ulla and Pulzer, Alina and Bluemel, Christina and Wild, Vanessa and Fassnacht, Martin and Steger, U.},
  title     = {A case report of a solitary pancreatic metastasis of an adrenocortical carcinoma},
  series = {BMC Surgery},
  volume    = {15},
  journal   = {BMC Surgery},
  number    = {93},
  doi       = {10.1186/s12893-015-0076-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126130},
  year      = {2015},
  abstract  = {Background Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin. Case presentation Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred. Conclusion Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.},
  language  = {en}
}
@phdthesis{Becker2010,
  author    = {Becker, Kilian},
  title     = {Entwicklung eines 3D-Ganzk{\"o}rper-Ultraschalls an Kleintieren f{\"u}r morphologische Bildgebung, Volumetrie und Bildfusion mit PET},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-55916},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Einleitung: Ultraschall wird seit mehr als 50 Jahren in der Medizin eingesetzt und ist mittlerweile ein unverzichtbares diagnostisches Verfahren, es erlaubt eine nicht-invasive Darstellung der Morphologie und Funktion von Organen in Echtzeit. In der Kleintierbildgebung dominieren bisher zur morphologischen Bildgebung Computertomographie (CT) und Magnetresonanztomographie (MRT). Daher wurde in der vorliegenden Arbeit die Idee entwickelt, die morphologischen Informationen des 3D-Ultraschalls (3D-US) f{\"u}r Untersuchungen an Kleintieren zu verwenden, außerdem sollten Methoden zur multimodalen Bildgebung und Bildfusion von 3D-US und Kleintier-Positronenemissionstomographie (PET) entwickelt werden. Der Vorteil des Ultraschalls gegen{\"u}ber dem Kleintier-CT liegt in der fehlenden Strahlenbelastung und der guten Verf{\"u}gbarkeit, was besonders f{\"u}r Verlaufsstudien von Interesse ist. Methoden und Ergebnisse: Zur Bildoptimierung wurde ein Fadenphantom entwickelt, welches aufgrund der feinen Strukturen die qualitative als auch quantitative Bestimmung der Aufl{\"o}sung erm{\"o}glicht. Die Vorarbeiten am Fadenphantom konnten exzellent die Probleme des 3D-Ultraschalls mit der achsenabh{\"a}ngigen Aufl{\"o}sung zeigen und erm{\"o}glichten eine schnelle Beurteilung der Bildqualit{\"a}t. Hier bestehen Einsatzm{\"o}glichkeiten in der Bewertung verschiedener Ultraschallger{\"a}te bez{\"u}glich der Tauglichkeit f{\"u}r 3D-Datenaquisition. Zur reproduzierbaren Lagerung von M{\"a}usen wurde eine Schallkopff{\"u}hrung ein sowohl f{\"u}r 3D-US als auch Kleintier-PET kompatibler Tierhalter entwickelt. Die Maus lag zur Untersuchung im angew{\"a}rmten Wasserbad auf dem Tierhalter fixiert, mit Inhalationsan{\"a}sthesie und Sauerstoff {\"u}ber eine Atemmaske versorgt. Der Zeitaufwand f{\"u}r eine 3D-US-Untersuchung betrug f{\"u}r die Akquisition etwa eine Minute. Die generierten Ultraschalldatens{\"a}tze waren von guter Qualit{\"a}t, Strukturen wie Leber, Nieren, Blase, Wirbels{\"a}ule und Lunge konnten selbst bei kleinen M{\"a}usen von unter 20 Gramm K{\"o}rpergewicht gut dargestellt werden. Zur Validierung des 3D-Ultraschalls wurde das Volumen verschiedener Organe und Tumore bestimmt und mit dem Goldstandard verglichen. Um die Koregistrierung mit der Kleintier-PET zu erm{\"o}glichen, wurden auf dem Tierhalter drei „fiducial markers" angebracht, die Position und Orientierung eindeutig definieren. Die Kleintier-PET-Untersuchungen wurden nach standardisierten Protokollen durchgef{\"u}hrt. Die anschließende Bildfusion erfolgte mittels der frei verf{\"u}gbaren Software "Amide". Diskussion: Mit dem in dieser Arbeit beschriebenen Verfahren ist eine standardisierte Gewinnung von 3D-US-Datens{\"a}tzen an Kleintieren m{\"o}glich; zus{\"a}tzlich konnte die Machbarkeit der Bildfusion mit PET-Datens{\"a}tzen gezeigt werden. Der Einsatz des 3D-Ultraschalls in longitudinalen Studien, zum Beispiel zur Beurteilung der Tumorprogression, ist vorstellbar. Die Zuverl{\"a}ssigkeit der volumetrischen Berechnungen ist f{\"u}r gr{\"o}ßere Organvolumina gut, bei kleineren Volumina besteht noch Optimierungsbedarf. Weitere Verbesserungen k{\"o}nnten durch den Einsatz von speziellen Schallk{\"o}pfen und h{\"o}heren Schallfrequenzen erzielt werden.},
  subject      = {Ultraschalldiagnostik},
  language  = {de}
}
@article{BeykanDamEberleinetal.2016,
  author    = {Beykan, Seval and Dam, Jan S. and Eberlein, Uta and Kaufmann, Jens and Kj{\ae}rgaard, Benedict and J{\o}dal, Lars and Bouterfa, Hakim and Bejot, Romain and Lassmann, Michael and Jensen, Svend Borup},
  title     = {\(^{177}\)Lu-OPS201 targeting somatostatin receptors: in vivo biodistribution and dosimetry in a pig model},
  series = {EJNMMI Research},
  volume    = {6},
  journal   = {EJNMMI Research},
  number    = {50},
  doi       = {10.1186/s13550-016-0204-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146888},
  year      = {2016},
  abstract  = {Background \(^{177}\)Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of \(^{177}\)Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications. Results \(^{177}\)Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 \% in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 \% of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq \(^{177}\)Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of 177Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels. Conclusions The \(^{177}\)Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range.},
  language  = {en}
}
@article{BeykanFaniJensenetal.2019,
  author    = {Beykan, Seval and Fani, Melpomeni and Jensen, Svend Borup and Nicolas, Guillaume and Wild, Damian and Kaufmann, Jens and Lassmann, Michael},
  title     = {In vivo biokinetics of \(^{177}\)Lu-OPS201 in Mice and Pigs as a Model for Predicting Human Dosimetry},
  series = {Contrast Media \& Molecular Imaging},
  volume    = {2019},
  journal   = {Contrast Media \& Molecular Imaging},
  doi       = {10.1155/2019/6438196},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177382},
  pages     = {6438196},
  year      = {2019},
  abstract  = {Introduction. \(^{177}\)Lu-OPS201 is a high-affinity somatostatin receptor subtype 2 antagonist for PRRT in patients with neuroendocrine tumors. The aim is to find the optimal scaling for dosimetry and to compare the biokinetics of \(^{177}\)Lu-OPS201 in animals and humans. Methods. Data on biokinetics of \(^{177}\)Lu-OPS201 were analyzed in athymic nude Foxn1\(^{nu}\) mice (28 F, weight: 26 ± 1 g), Danish Landrace pigs (3 F-1 M, weight: 28 ± 2 kg), and patients (3 F-1 M, weight: 61 ± 17 kg) with administered activities of 0.19-0.27 MBq (mice), 97-113 MBq (pigs), and 850-1086 MBq (patients). After euthanizing mice (up to 168 h), the organ-specific activity contents (including blood) were measured. Multiple planar and SPECT/CT scans were performed until 250 h (pigs) and 72 h (patients) to quantify the uptake in the kidneys and liver. Blood samples were taken up to 23 h (patients) and 300 h (pigs). In pigs and patients, kidney protection was applied. Time-dependent uptake data sets were created for each species and organ/tissue. Biexponential fits were applied to compare the biokinetics in the kidneys, liver, and blood of each species. The time-integrated activity coefficients (TIACs) were calculated by using NUKFIT. To determine the optimal scaling, several methods (relative mass scaling, time scaling, combined mass and time scaling, and allometric scaling) were compared. Results. A fast blood clearance of the compound was observed in the first phase (<56 h) for all species. In comparison with patients, pigs showed higher liver retention. Based on the direct comparison of the TIACs, an underestimation in mice (liver and kidneys) and an overestimation in pigs' kidneys compared to the patient data (kidney TIAC: mice = 1.4 h, pigs = 7.7 h, and patients = 5.8 h; liver TIAC: mice = 0.7 h, pigs = 4.1 h, and patients = 5.3 h) were observed. Most similar TIACs were obtained by applying time scaling (mice) and combined scaling (pigs) (kidney TIAC: mice = 3.9 h, pigs = 4.8 h, and patients = 5.8 h; liver TIAC: mice = 0.9 h, pigs = 4.7 h, and patients = 5.3 h). Conclusion. If the organ mass ratios between the species are high, the combined mass and time scaling method is optimal to minimize the interspecies differences. The analysis of the fit functions and the TIACs shows that pigs are better mimicking human biokinetics.},
  language  = {en}
}
@phdthesis{Blasl2004,
  author    = {Blasl, Christiana},
  title     = {Chromatografischer Nachweis endogen radioiodierter Verbindungen im Urin von Patienten mit differenziertem Schilddr{\"u}senkarzinom nach Iod-131-Ganzk{\"o}rperszintigrafie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-12726},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Der Follow-UP von Patienten mit differenziertem Schilddr{\"u}senkarzinom (DTC) wird konventionell mit I-131-Ganzk{\"o}rperzintigrafie (GKS) und Bestimmung des Serumthyreoglobulins (hTg) durchgef{\"u}hrt. Wegen der Inzidenz von 15\%-20\% diskordanter Resultate entwickelte Bianchi et al. (J Nucl Med 1993; 34: 2032-2037) die Serumchromatografie von endogen radioiodiertem Triiodthyronin (L-T3) und Thyroxin (L-T4) bei Patienten mit DTC nach oraler Applikation von I-131. Da im Rahmen des Iodstoffwechsels auch radioiodierte Verbindungen im Urin erscheinen, versuchten wir eine Urinchromatografiemethode zu entwickeln, basierend auf der Annahme, dass ein pathologischer I-131-Uptake, wenngleich zu niedrig um im GKS erkannt zu werden, gleichwohl {\"u}ber endogen iodierte Schilddr{\"u}senprodukte im Urin nachgewiesen werden kann. In der Urinchromatografie konnten die Ergebnisse der Serumchromatografie nicht erreicht werden.},
  language  = {de}
}
@article{BluemelLinkeHerrmannetal.2016,
  author    = {Bluemel, Christina and Linke, Fraenze and Herrmann, Ken and Simunovic, Iva and Eiber, Matthias and Kestler, Christian and Buck, Andreas K. and Schirbel, Andreas and Bley, Thorsten A. and Wester, Hans-Juergen and Vergho, Daniel and Becker, Axel},
  title     = {Impact of \(^{68}\)Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy},
  series = {EJNMMI Research},
  volume    = {6},
  journal   = {EJNMMI Research},
  number    = {78},
  doi       = {10.1186/s13550-016-0233-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147798},
  year      = {2016},
  abstract  = {Background Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning. Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity. Results Suspicious lesions were detected in 24/45 (53.3 \%) patients. In 62.5 \% of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 \%) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 \%) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 \%) within a mean follow-up of 8.12 ± 5.23 months. Conclusions \(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 \% of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT.},
  language  = {en}
}
@article{BreunMonoranuKessleretal.2019,
  author    = {Breun, Maria and Monoranu, Camelia M. and Kessler, Almuth F. and Matthies, Cordula and L{\"o}hr, Mario and Hagemann, Carsten and Schirbel, Andreas and Rowe, Steven P. and Pomper, Martin G. and Buck, Andreas K. and Wester, Hans-J{\"u}rgen and Ernestus, Ralf-Ingo and Lapa, Constantin},
  title     = {[\(^{68}\)Ga]-Pentixafor PET/CT for CXCR4-mediated imaging of vestibular schwannomas},
  series = {Frontiers in Oncology},
  volume    = {9},
  journal   = {Frontiers in Oncology},
  number    = {503},
  doi       = {10.3389/fonc.2019.00503},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201863},
  year      = {2019},
  abstract  = {We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor. Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients. Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors. Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.},
  language  = {en}
}
@phdthesis{BrumberggebIchouh2019,
  author    = {Brumberg [geb. Ichouh], Dalma},
  title     = {\(^{11}\)C-MET und \(^{18}\)F-FDG: \(In\) \(vitro\) Vergleich zur Bildgebung beim Multiplen Myelom im Kontext biologischer Charakteristika},
  doi       = {10.25972/OPUS-18184},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181843},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Das Multiple Myelom ist eine h{\"a}matologische Erkrankung, die durch die Proliferation von Plasmazellen und die Produktion von Antik{\"o}rpern oder deren Leichtketten gekennzeichnet ist. Eine fr{\"u}he Diagnosestellung durch Detektion sowohl intra- als auch extramedull{\"a}rer Manifestationen ist f{\"u}r die Einleitung einer effektiven Therapie von entscheidender Bedeutung. Ebenso bedeutsam ist ein wirksames Therapiemonitoring. Wichtige diagnostische Modalit{\"a}ten sind bei beiden Fragestellungen tomografische, bildgebende Verfahren. Hierbei wurde die Effektivit{\"a}t der 18F-FDG-PET/CT im Rahmen der Diagnose, des Stagings und der Prognoseabsch{\"a}tzung bereits nachgewiesen. Dennoch ist ihr klinischer Nutzen durch die geringe Sensitivit{\"a}t bei Detektion von diffusem Knochenmarksbefall und Vorliegen sowohl falsch positiver als auch falsch negativer Befunde limitiert. Die vorliegende Arbeit hat untersucht, ob der aminos{\"a}urebasierte Tracer 11C-MET {\"u}ber spezifische Eigenschaften verf{\"u}gt, die eine h{\"o}here Sensitivit{\"a}t und Spezifit{\"a}t in der Detektion von Myelomzellen erm{\"o}glichen und ob der Radioligand dem etablierten Glukoseanalogon 18F-FDG {\"u}berlegen ist. Hierf{\"u}r wurden drei etablierte humane Myelomzelllinien, sowohl nativ als auch nach 48-st{\"u}ndiger Therapie mit dem Proteasominhibitor Carfilzomib, mit 18F-FDG und 11C-MET inkubiert und mithilfe eines Gammastrahlungsz{\"a}hlers beurteilt. Zudem wurde untersucht, ob die Traceraufnahme mit spezifischen Charakteristika der Tumorbiologie korreliert. So wurde die Oberfl{\"a}chenexpression von CD138 und CXCR4, die intrazellul{\"a}re Expression der Leichtketten κ/λ und die Proliferation der Zelllinien mittels Durchflusszytometrie vor und nach Behandlung mit Carfilzomib eruiert. Die unbehandelten Zellen zeigten, verglichen zu 18F-FDG, bereits nach k{\"u}rzester Inkubationsdauer eine 3-3,5-fach h{\"o}here 11C-MET Retention. Weiterhin zeigte sich die 11C-MET-Aufnahme nach Behandlung aller Zellreihen insgesamt marginal h{\"o}her als die 18F-FDG-Aufnahme, w{\"a}hrend die Reduktion der 11C-MET-Anreicherung im pr{\"a}- zu posttherapeutischen Vergleich f{\"u}r alle drei Zelllinien signifikant war. Eine m{\"o}gliche Erkl{\"a}rung f{\"u}r diese Beobachtungen liefert die Myelombiologie: eine erh{\"o}hte Aufnahme der radioaktiv markierten Aminos{\"a}ure durch MM-Zellen k{\"o}nnte durch eine Zunahme der Zellproliferation und insbesondere durch eine Steigerung der Proteinsynthese im Rahmen der {\"u}berschießenden Produktion von M-Protein bedingt sein. In Zusammenschau k{\"o}nnte 11C-MET mit h{\"o}herer Sensitivit{\"a}t Myelommanifestationen detektieren, wodurch ggf. L{\"a}sionen mit geringem Metabolismus dargestellt und eine bessere Beurteilung des Krankheitspogresses erfolgen k{\"o}nnte. Zudem bietet f{\"u}r den klinischen Einsatz die - verglichen zu 18F-FDG - gr{\"o}ßere Differenz der 11C-MET-Retention zwischen pr{\"a}- und posttherapeutischer Messung die M{\"o}glichkeit einer besseren Beurteilbarkeit des Therapieansprechens. 11C-MET birgt ggf. das Potential auch minimale aktive Restherde zu detektieren und damit Patienten einem individualisierten Therapiekonzept zuzuf{\"u}hren. Ein Zusammenhang zwischen den untersuchten Biomarkern und der 11C-MET Retention bzw. deren Abnahme nach Behandlung konnte nicht gezeigt werden. Somit sollten f{\"u}r 11C-MET andere Biomarker herangezogen werden, um diese mit der Bildgebung zu korrelieren und zu bewerten.},
  subject      = {Multiples Myelom},
  language  = {de}
}
@article{BrumbergBecklDierksetal.2020,
  author    = {Brumberg, Joachim and Beckl, Melanie and Dierks, Alexander and Schirbel, Andreas and Krebs, Markus and Buck, Andreas and K{\"u}bler, Hubert and Lapa, Constantin and Seitz, Anna Katharina},
  title     = {Detection Rate of \(^{68}\)Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy},
  series = {Biomedicines},
  volume    = {8},
  journal   = {Biomedicines},
  number    = {11},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines8110511},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219301},
  year      = {2020},
  abstract  = {Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on the detection rate of \(^{68}\)Ga-PSMA ligand PET/CT. Thus, 399 patients with initial radical prostatectomy and 68Ga-PSMA ligand PET/CT during PSA relapse were retrospectively evaluated. Propensity score matching was used to create two balanced groups of 62 subjects who either did or did not receive ADT within six months before imaging. All \(^{68}\)Ga-PSMA ligand PET/CT were evaluated visually and with semiquantitative measures. The detection rate of tumor recurrence was significantly higher in the group with ADT (88.7\% vs. 72.6\%, p = 0.02) and improved with increasing PSA-levels in both groups. In subjects with pathological PET/CT and ADT, whole-body total lesion PSMA (p < 0.01) and PSMA-derived tumor volume (p < 0.01) were significantly higher than in those without ADT. More PSMA-positive lesions and higher PSMA-derived volumetric parameters in patients with ADT suggest that a better detection rate is related to a (biologically) more advanced disease stage. Due to high detection rates in patients with PSA-levels < 2 ng/mL, the withdrawal of ADT before PSMA ligand PET/CT cannot be recommended.},
  language  = {en}
}
@article{BrumbergBlazhenetsSchroeteretal.2019,
  author    = {Brumberg, Joachim and Blazhenets, Ganna and Schr{\"o}ter, Nils and Frings, Lars and Jost, Wolfgang H. and Lapa, Constantin and Meyer, Philipp T.},
  title     = {Imaging cardiac sympathetic innervation with MIBG: linear conversion of the heart-to-mediastinum ratio between different collimators},
  series = {EJNMMI Physics},
  volume    = {6},
  journal   = {EJNMMI Physics},
  doi       = {10.1186/s40658-019-0250-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221675},
  year      = {2019},
  abstract  = {Background The heart-to-mediastinum (H/M) ratio is a commonly used parameter to measure cardiac I-123 metaiodobenzylguanidine (MIBG) uptake. Since the H/M ratio is substantially influenced by the collimator type, we investigated whether an empirical linear conversion of H/M ratios between camera systems with low-energy (LE) and medium-energy (ME) collimator is possible. Methods We included 18 patients with parkinsonism who were referred to one of the two participating molecular imaging facilities for the evaluation of cardiac sympathetic innervation by MIBG scintigraphy. Two consecutive planar image datasets were acquired with LE and ME collimators at 4 h after MIBG administration. Linear regression analyses were performed to describe the association between the H/M ratios gained with both collimator settings, and the accuracy of a linear transfer of the H/M ratio between collimators and across centers was assessed using a leave-one-out procedure. Results H/M ratios acquired with LE and ME collimators showed a strong linear relationship both within each imaging facility (R\(^2\) = 0.99, p < 0.001 and R\(^2\) = 0.90, p < 0.001) and across centers (H/M-LE = 0.41 × H/M-ME + 0.63, R\(^2\) = 0.97, p < 0.001). A linear conversion of H/M ratios between collimators and across centers was estimated to be very accurate (mean absolute error 0.05 ± 0.04; mean relative absolute error 3.2 ± 2.6\%). Conclusions The present study demonstrates that a simple linear conversion of H/M ratios acquired with different collimators is possible with high accuracy. This should greatly facilitate the exchange of normative data between settings and pooling of data from different institutions.},
  language  = {en}
}
@article{BrumbergKuzkinaLapaetal.2021,
  author    = {Brumberg, Joachim and Kuzkina, Anastasia and Lapa, Constantin and Mammadova, Sona and Buck, Andreas and Volkmann, Jens and Sommer, Claudia and Isaias, Ioannis U. and Doppler, Kathrin},
  title     = {Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy},
  series = {Neurobiology of Disease},
  volume    = {153},
  journal   = {Neurobiology of Disease},
  doi       = {10.1016/j.nbd.2021.105332},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260061},
  pages     = {105332},
  year      = {2021},
  abstract  = {Pathological aggregates of alpha-synuclein in peripheral dermal nerve fibers can be detected in patients with idiopathic Parkinson's disease and multiple system atrophy. This study combines skin biopsy staining for p-alpha-synuclein depositions and radionuclide imaging of the heart with [\(^{123}\)I]-metaiodobenzylguanidine to explore peripheral denervation in both diseases. To this purpose, 42 patients with a clinical diagnosis of Parkinson's disease or multiple system atrophy were enrolled. All patients underwent a standardized clinical workup including neurological evaluation, neurography, and blood samples. Skin biopsies were obtained from the distal and proximal leg, back, and neck for immunofluorescence double labeling with anti-p-alpha-synuclein and anti-PGP9.5. All patients underwent myocardial [\(^{123}\)I]-metaiodobenzylguanidine scintigraphy. Dermal p-alpha-synuclein was observed in 47.6\% of Parkinson's disease patients and was mainly found in autonomic structures. 81.0\% of multiple system atrophy patients had deposits with most of cases in somatosensory fibers. The [\(^{123}\)I]-metaiodobenzylguanidine heart-to-mediastinum ratio was lower in Parkinson's disease than in multiple system atrophy patients (1.94 +/- 0.63 vs. 2.91 +/- 0.96; p < 0.0001). Irrespective of the diagnosis, uptake was lower in patients with than without p-alpha-synuclein in autonomic structures (1.42 +/- 0.51 vs. 2.74 +/- 0.83; p < 0.0001). Rare cases of Parkinson's disease with p-alpha-synuclein in somatosensory fibers and multiple system atrophy patients with deposits in autonomic structures or both fiber types presented with clinically overlapping features. In conclusion, this study suggests that alpha-synuclein contributes to peripheral neurodegeneration and mediates the impairment of cardiac sympathetic neurons in patients with synucleinopathies. Furthermore, it indicates that Parkinson's disease and multiple system atrophy share pathophysiologic mechanisms of peripheral nervous system dysfunction with a clinical overlap.},
  language  = {en}
}
@article{BrumbergKuestersAlMomanietal.2017,
  author    = {Brumberg, Joachim and K{\"u}sters, Sebastian and Al-Momani, Ehab and Marotta, Giorgio and Cosgrove, Kelly P. and van Dyck, Christopher H. and Herrmann, Ken and Homola, Gy{\"o}rgy A. and Pezzoli, Gianni and Buck, Andreas K. and Volkmann, Jens and Samnick, Samuel and Isaias, Ioannis U.},
  title     = {Cholinergic activity and levodopa-induced dyskinesia: a multitracer molecular imaging study},
  series = {Annals of Clinical and Translational Neurology},
  volume    = {4},
  journal   = {Annals of Clinical and Translational Neurology},
  number    = {9},
  doi       = {10.1002/acn3.438},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170406},
  pages     = {632-639},
  year      = {2017},
  abstract  = {Objective: To investigate the association between levodopa-induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease. Methods: This study included 13 Parkinson's disease patients with peak-of-dose levodopa-induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5-[\(^{123}\)I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine single-photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [\(^{123}\)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography, to measure dopamine reuptake transporter density and 2-[\(^{18}\)F]fluoro-2-deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed. Results: Density of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side. Interpretation: Our findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic-depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression.},
  language  = {en}
}
@article{BrumbergSchroeterBlazhenetsetal.2020,
  author    = {Brumberg, Joachim and Schr{\"o}ter, Nils and Blazhenets, Ganna and Frings, Lars and Volkmann, Jens and Lapa, Constantin and Jost, Wolfgang H. and Isaias, Ioannis U. and Meyer, Philipp T.},
  title     = {Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy},
  series = {NPJ Parkinsons Disease},
  volume    = {6},
  journal   = {NPJ Parkinsons Disease},
  doi       = {10.1038/s41531-020-00141-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230675},
  year      = {2020},
  abstract  = {[\(^{18}\)F]fluorodeoxyglucose (FDG) PET and [\(^{123}\)I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 +/- 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator \#1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater \#1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred.},
  language  = {en}
}
@article{BuckDecristoforo2016,
  author    = {Buck, Andreas and Decristoforo, Clemens},
  title     = {Highlights lecture EANM 2015: the search for nuclear medicine's superheroes},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {43},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {10},
  doi       = {10.1007/s00259-016-3423-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187613},
  pages     = {1910-1927},
  year      = {2016},
  abstract  = {The EANM 2015 Annual Congress, held from October 10th to 14th in Hamburg, Germany, was outstanding in many respects. With 5550 participants, this was by far the largest European congress concerning nuclear medicine. More than 1750 scientific presentations were submitted, with more than 250 abstracts from young scientists, indicating that the future success of our discipline is fuelled by a high number of young individuals becoming involved in a multitude of scientific activities. Significant improvements have been made in molecular imaging of cancer, particularly in prostate cancer. PSMA-directed PET/CT appears to become a new gold standard for staging and restaging purposes. Novel tumour specific compounds have shown their potential for target identification also in other solid neoplasms and further our understanding of tumour biology and heterogeneity. In addition, a variety of nuclear imaging techniques guiding surgical interventions have been introduced. A particular focus of the congress was put on targeted, radionuclide based therapies. Novel theranostic concepts addressing also tumour entities with high incidence rates such as prostate cancer, melanoma, and lymphoma, have shown effective anti-tumour activity. Strategies have been presented to improve further already established therapeutic regimens such as somatostatin receptor based radio receptor therapy for treating advanced neuroendocrine tumours. Significant contributions were presented also in the neurosciences track. An increasing number of target structures of high interest in neurology and psychiatry are now available for PET and SPECT imaging, facilitating specific imaging of different subtypes of dementia and movement disorders as well as neuroinflammation. Major contributions in the cardiovascular track focused on further optimization of cardiac perfusion imaging by reducing radiation exposure, reducing scanning time, and improving motion correction. Besides coronary artery disease, many contributions focused on cardiac inflammation, cardiac sarcoidosis, and specific imaging of large vessel vasculitis. The physics and instrumentation track included many highlights such as novel, high resolution scanners. The most noteworthy news and developments of this meeting were summarized in the highlights lecture. Only 55 scientific contributions were mentioned, and hence they represent only a brief summary, which is outlined in this article. For a more detailed view, all presentations can be accessed by the online version of the European Journal of Nuclear Medicine and Molecular Imaging (Volume 42, Supplement 1).},
  language  = {en}
}
@article{BuckSerflingLindneretal.2022,
  author    = {Buck, Andreas K. and Serfling, Sebastian E. and Lindner, Thomas and H{\"a}nscheid, Heribert and Schirbel, Andreas and Hahner, Stefanie and Fassnacht, Martin and Einsele, Hermann and Werner, Rudolf A.},
  title     = {CXCR4-targeted theranostics in oncology},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {12},
  doi       = {10.1007/s00259-022-05849-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324545},
  pages     = {4133-4144},
  year      = {2022},
  abstract  = {A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.},
  language  = {en}
}
@article{BuderLapaKreissletal.2014,
  author    = {Buder, Kristina and Lapa, Constantin and Kreissl, Michael C. and Schirbel, Andreas and Herrmann, Ken and Schnack, Alexander and Br{\"o}cker, Eva-Bettina and Goebeler, Matthias and Buck, Andreas K. and Becker, J{\"u}rgen C.},
  title     = {"Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging"},
  doi       = {10.1186/1471-2407-14-268},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110326},
  year      = {2014},
  abstract  = {Background Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm with increasing incidence, aggressive behavior and poor prognosis. Somatostatin receptors (SSTR) are expressed in MCC and represent a potential target for both imaging and treatment. Methods To non-invasively assess SSTR expression in MCC using PET and the radiotracers [68Ga]DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) or -octreotate (DOTATATE) as surrogate for tumor burden. In 24 patients with histologically proven MCC SSTR-PET was performed and compared to results of computed tomography (CT). Results SSTR-PET detected primary and metastatic MCC lesions. On a patient-based analysis, sensitivity of SSTR-PET was 73\% for nodal metastases, 100\% for bone, and 67\% for soft-tissue metastases, respectively. Notably, brain metastases were initially detected by SSTR-PET in 2 patients, whereas liver and lung metastases were diagnosed exclusively by CT. SSTR-PET showed concordance to CT results in 20 out of 24 patients. Four patients (17\%) were up-staged due to SSTR-PET and patient management was changed in 3 patients (13\%). Conclusion SSTR-PET showed high sensitivity for imaging bone, soft tissue and brain metastases, and particularly in combination with CT had a significant impact on clinical stage and patient management.},
  language  = {en}
}
@phdthesis{Boegelein2021,
  author    = {B{\"o}gelein, Anna},
  title     = {Einfluss systemischer Therapeutika auf die CXCR4-Expression von Myelomzellen},
  doi       = {10.25972/OPUS-24174},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241746},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Im Zuge der Bem{\"u}hungen um neue, tumorspezifische Therapieans{\"a}tze f{\"u}r die Myelomerkrankung hat sich der C-X-C-Chemokinrezeptor 4 (CXCR4) aufgrund seiner zentralen Rolle in der Tumorgenese als vielversprechender Angriffspunkt hervorgetan. Im Sinne eines theranostischen Konzepts wird der Rezeptor mithilfe eines radioaktiv markierten Liganden quantifiziert und anschließend von rezeptorspezifischen Radiotherapeutika als Zielstruktur genutzt. Die CXCR4-Expression ist allerdings ein h{\"o}chst dynamischer Prozess mit großer inter- und intraindividueller Heterogenit{\"a}t, der u.a. durch eine begleitende Chemotherapie beeinflusst werden kann. Ob sich therapieinduzierte Ver{\"a}nderungen der Rezeptorexpression gezielt nutzen lassen, um die CXCR4-Expression zu optimieren und so die Effektivit{\"a}t der CXCR4-gerichteten Strategien zu steigern, wurde bislang nicht untersucht. Vor diesem Hintergrund wurden in der vorliegenden Arbeit verschiedene, in der Myelomtherapie etablierte Substanzen sowohl einzeln als auch in Kombination hinsichtlich ihres Einflusses auf die CXCR4-Expression von MM-Zelllinien und prim{\"a}ren MM-Zellen unter in vitro Bedingungen analysiert. In den durchgef{\"u}hrten Experimenten zeigte sich eine hohe Variabilit{\"a}t der CXCR4-Expression der MM-Zellen nach Therapieinduktion, die sich als substanz-, dosis- und zeitabh{\"a}ngig herausstellte. Die Ergebnisse best{\"a}tigten das große Potenzial der therapieinduzierten Modulation der CXCR4-Expression. Im weiteren Verlauf sind translationale Forschungsans{\"a}tze gerechtfertigt, die die {\"U}bertragbarkeit der in vitro gewonnenen Ergebnisse auf die komplexen Vorg{\"a}nge im lebenden Organismus {\"u}berpr{\"u}fen. Langfristiges Ziel ist der Entwurf eines patientenzentrierten, multimodalen Therapiekonzepts, welches das CXCR4-gerichtete theranostische Konzept mit einer individuell angepassten, medikament{\"o}sen MM-Therapie kombiniert.},
  subject      = {Plasmozytom},
  language  = {de}
}
@phdthesis{Boeser2024,
  author    = {B{\"o}ser, Janis},
  title     = {Einfluss der PSMA-PET/CT auf das psychische Befinden von Patienten mit Prostatakarzinom},
  doi       = {10.25972/OPUS-35204},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-352046},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Das fr{\"u}hzeitige Erkennen psychoonkologischer Belastungen ist Bestandteil des optimalen therapeutischen Managements von Tumorpatienten. Nur wenige, widerspr{\"u}chliche Studien untersuchten bisher das psychische Befinden im Verlauf einer PET/CT. Bezogen auf das Prostatakarzinom gibt es bislang keine spezifische Studie, obwohl es die h{\"a}ufigste onkologische Erkrankung des Mannes darstellt. Aufgrund der insgesamt guten Prognose wird von einer geringeren psychischen Belastung ausgegangen. Mithilfe dieser Studie sollte durch Kombination etablierter Frageb{\"o}gen das psychische Befinden im Verlauf der PET/CT explorativ untersucht werden. Von Oktober 2018 bis Februar 2020 wurde 531 m{\"a}nnlichen Patienten der Nuklearmedizin des Universit{\"a}tsklinikums W{\"u}rzburg die Teilnahme angeboten. N = 85 Patienten (n = 38 Patienten mit Prostatakarzinom sowie n = 47 Patienten mit anderen malignen Erkrankungen) stimmten einer vollst{\"a}ndigen Teilnahme zu. Es wurden zwei Messzeitpunkte (T1 nach Durchf{\"u}hrung der PET/CT; T2 nach Ergebnismitteilung) festgelegt. Als Messinstrumente wurden der PA-F-KF, QUICC, DT, STAI-X1, PANAS und ein Selbsteinsch{\"a}tzungsbogen verwendet. 24 \% (T1) bzw. 35 \% (T2) der Patienten mit Prostatakarzinom gaben eine dysfunktionale Progredienzangst an, 55 \% (T1+T2) eine pathologische psychische Belastung. 53 \% (T1) bzw. 50 \% (T2) der Patienten zeigten eine relevant erh{\"o}hte Zustandsangst. Die Progredienzangst stieg nach Ergebnismitteilung an (p = 0,048; η² = 0,106), die Ungewissheit {\"u}ber den Stand der Erkrankung (p = 0,014; η² = 0,165) und Bew{\"a}ltigbarkeit des Alltags (p = 0,016; η² = 0,163) reduzierten sich. Allgemeine {\"A}ngste wie die Zustandsangst, der Distress und negative Affekte ver{\"a}nderten sich nicht. PSA-Werte ohne bildmorphologisches Korrelat l{\"o}sten eine gr{\"o}ßere Unsicherheit bez{\"u}glich des aktuellen Krankheitszustandes aus (p = 0,029; η² = 0,128). J{\"u}ngere Patienten zeigten vor (p = 0,005; η² = 0,207) und nach (p = 0,001; η² = 0,290) Ergebnismitteilung eine h{\"o}here Angst um ihre Berufst{\"a}tigkeit und gaben eine geringere Erleichterung nach Ergebnismitteilung (p = 0,016; η² = 0,165) an. Als Limitationen sind die geringe Fallzahl und Teilnahmequote, multiple Testung und fehlende Erfragung psychischer Erkrankungen zu beachten. Insgesamt zeigen sich eine hohe psychische Belastung und {\"A}ngste im Verlauf der PET/CT. Patienten mit Prostatakarzinom sind zu diesem Zeitpunkt nicht weniger belastet als Patienten mit anderen malignen Erkrankungen.},
  subject      = {Angst},
  language  = {de}
}
@article{CanessaPozziArnulfoetal.2016,
  author    = {Canessa, Andrea and Pozzi, Nicol{\`o} G. and Arnulfo, Gabriele and Brumberg, Joachim and Reich, Martin M. and Pezzoli, Gianni and Ghilardi, Maria F. and Matthies, Cordula and Steigerwald, Frank and Volkmann, Jens and Isaias, Ioannis U.},
  title     = {Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations and Cortical-Subcortical Coupling during Movements: Preliminary Evidence in Subjects with Parkinson's Disease},
  series = {Frontiers in Human Neuroscience},
  volume    = {10},
  journal   = {Frontiers in Human Neuroscience},
  number    = {611},
  doi       = {10.3389/fnhum.2016.00611},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164061},
  year      = {2016},
  abstract  = {Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson's disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement.},
  language  = {en}
}
@article{ChenHiranoWerneretal.2018,
  author    = {Chen, Xinyu and Hirano, Mitsuru and Werner, Rudolf A. and Decker, Michael and Higuchi, Takahiro},
  title     = {Novel \(^{18}\)F-labeled PET Imaging Agent FV45 targeting the Renin-Angiotensin System},
  series = {ACS Omega},
  volume    = {3},
  journal   = {ACS Omega},
  number    = {9},
  issn      = {2470-1343},
  doi       = {10.1021/acsomega.8b01885},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167144},
  pages     = {10460-10470},
  year      = {2018},
  abstract  = {Renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure and hormonal balance. Using positron emission tomography (PET) technology, it is possible to monitor the physiological and pathological distribution of angiotensin II type 1 receptors (AT\(_1\)), which reflects the functionality of RAS. A new \(^{18}\)F-labeled PET tracer derived from the clinically used AT\(_1\) antagonist valsartan showing the least possible chemical alteration from the valsartan structure has been designed and synthesized with several strategies, which can be applied for the syntheses of further derivatives. Radioligand binding study showed that the cold reference FV45 (K\(_i\) 14.6 nM) has almost equivalent binding affinity as its lead valsartan (K\(_i\) 11.8 nM) and angiotensin II (K\(_i\) 1.7 nM). Successful radiolabeling of FV45 in a one-pot radiofluorination followed by the deprotection procedure with 21.8 ± 8.5\% radiochemical yield and >99\% radiochemical purity (n = 5) enabled a distribution study in rats and opened a path to straightforward large-scale production. A fast and clear kidney uptake could be observed, and this renal uptake could be selectively blocked by pretreatment with AT\(_1\)-selective antagonist valsartan. Overall, as the first \(^{18}\)F-labeled PET tracer based on a derivation from clinically used drug valsartan with almost identical chemical structure, [\(^{18}\)F]FV45 will be a new tool for assessing the RAS function by visualizing AT\(_i\) receptor distributions and providing further information regarding cardiovascular system malfunction as well as possible applications in inflammation research and cancer diagnosis.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{ChenKudoLapaetal.2020,
  author    = {Chen, Xinyu and Kudo, Takashi and Lapa, Constantin and Buck, Andreas and Higuchi, Takahiro},
  title     = {Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements},
  series = {Journal of Neural Transmission},
  volume    = {127},
  journal   = {Journal of Neural Transmission},
  doi       = {10.1007/s00702-020-02180-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241148},
  pages     = {851-873},
  year      = {2020},
  abstract  = {The norepinephrine transporter (NET) is a major target for the evaluation of the cardiac sympathetic nerve system in patients with heart failure and Parkinson's disease. It is also used in the therapeutic applications against certain types of neuroendocrine tumors, as exemplified by the clinically used \(^{123/131}\)I-MIBG as theranostic single-photon emission computed tomography (SPECT) agent. With the development of more advanced positron emission tomography (PET) technology, more radiotracers targeting NET have been reported, with superior temporal and spatial resolutions, along with the possibility of functional and kinetic analysis. More recently, fluorine-18-labelled NET tracers have drawn increasing attentions from researchers, due to their longer radiological half-life relative to carbon-11 (110 min vs. 20 min), reduced dependence on on-site cyclotrons, and flexibility in the design of novel tracer structures. In the heart, certain NET tracers provide integral diagnostic information on sympathetic innervation and the nerve status. In the central nervous system, such radiotracers can reveal NET distribution and density in pathological conditions. Most radiotracers targeting cardiac NET-function for the cardiac application consistent of derivatives of either norepinephrine or MIBG with its benzylguanidine core structure, e.g. \(^{11}\)C-HED and \(^{18}\)F-LMI1195. In contrast, all NET tracers used in central nervous system applications are derived from clinically used antidepressants. Lastly, possible applications of NET as selective tracers over organic cation transporters (OCTs) in the kidneys and other organs controlled by sympathetic nervous system will also be discussed.},
  language  = {en}
}
@article{ChenWernerJavadietal.2015,
  author    = {Chen, Xinyu and Werner, Rudolf A. and Javadi, Mehrbod S. and Maya, Yoshifumi and Decker, Michael and Lapa, Constantin and Herrmann, Ken and Higuchi, Takahiro},
  title     = {Radionuclide imaging of neurohormonal system of the heart},
  series = {Theranostics},
  volume    = {5},
  journal   = {Theranostics},
  number    = {6},
  doi       = {10.7150/thno.10900},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149205},
  pages     = {545-558},
  year      = {2015},
  abstract  = {Heart failure is one of the growing causes of death especially in developed countries due to longer life expectancy. Although many pharmacological and instrumental therapeutic approaches have been introduced for prevention and treatment of heart failure, there are still limitations and challenges. Nuclear cardiology has experienced rapid growth in the last few decades, in particular the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET), which allow non-invasive functional assessment of cardiac condition including neurohormonal systems involved in heart failure; its application has dramatically improved the capacity for fundamental research and clinical diagnosis. In this article, we review the current status of applying radionuclide technology in non-invasive imaging of neurohormonal system in the heart, especially focusing on the tracers that are currently available. A short discussion about disadvantages and perspectives is also included.},
  language  = {en}
}
@article{ChenWernerKoshinoetal.2022,
  author    = {Chen, Xinyu and Werner, Rudolf A. and Koshino, Kazuhiro and Nose, Naoko and M{\"u}hlig, Saskia and Rowe, Steven P. and Pomper, Martin G. and Lapa, Constantin and Decker, Michael and Higuchi, Takahiro},
  title     = {Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity - Introducing High NET Affinity PET Probe \(^{18}\)F-AF78},
  series = {Theranostics},
  volume    = {12},
  journal   = {Theranostics},
  number    = {9},
  doi       = {10.7150/thno.63205},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300685},
  pages     = {4446 -- 4458},
  year      = {2022},
  abstract  = {Background: Radiolabeled agents that are substrates for the norepinephrine transporter (NET) can be used to quantify cardiac sympathetic nervous conditions and have been demonstrated to identify high-risk congestive heart failure (HF) patients prone to arrhythmic events. We aimed to fully characterize the kinetic profile of the novel \(^{18}\)F-labeled NET probe AF78 for PET imaging of the cardiac sympathetic nervous system (SNS) among various species. Methods: \(^{18}\)F-AF78 was compared to norepinephrine (NE) and established SNS radiotracers by employing in vitro cell assays, followed by an in vivo PET imaging approach with healthy rats, rabbits and nonhuman primates (NHPs). Additionally, chase protocols were performed in NHPs with NET inhibitor desipramine (DMI) and the NE releasing stimulator tyramine (TYR) to investigate retention kinetics in cardiac SNS. Results: Relative to other SNS radiotracers, 18F-AF78 showed higher transport affinity via NET in a cell-based competitive uptake assay (IC\(^{50}\) 0.42 ± 0.14 µM), almost identical to that of NE (IC\(^{50}\), 0.50 ± 0.16 µM, n.s.). In rabbits and NHPs, initial cardiac uptake was significantly reduced by NET inhibition. Furthermore, cardiac tracer retention was not affected by a DMI chase protocol but was markedly reduced by intermittent TYR chase, thereby suggesting that \(^{18}\)F-AF78 is stored and can be released via the synaptic vesicular turnover process. Computational modeling hypothesized the formation of a T-shaped π-π stacking at the binding site, suggesting a rationale for the high affinity of \(^{18}\)F-AF78. Conclusion: \(^{18}\)F-AF78 demonstrated high in vitro NET affinity and advantageous in vivo radiotracer kinetics across various species, indicating that \(^{18}\)F-AF78 is an SNS imaging agent with strong potential to guide specific interventions in cardiovascular medicine.},
  language  = {en}
}
@article{ChenWernerLapaetal.2018,
  author    = {Chen, Xinyu and Werner, Rudolf A. and Lapa, Constantin and Nose, Naoko and Hirano, Mitsuru and Javadi, Mehrbod S. and Robinson, Simon and Higuchi, Takahiro},
  title     = {Subcellular storage and release mode of the novel \(^{18}\)F-labeled sympathetic nerve PET tracer LMI1195},
  series = {EJNMMI Research},
  volume    = {8},
  journal   = {EJNMMI Research},
  number    = {12},
  issn      = {2191-219X},
  doi       = {10.1186/s13550-018-0365-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167081},
  year      = {2018},
  abstract  = {Background: \(^{18}\)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (\(^{18}\)F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intracellular behavior is not yet fully understood. The aim of the present study is to verify whether it is taken up in storage vesicles and released in company with vesicle turnover. Results: Both vesicle-rich (PC12) and vesicle-poor (SK-N-SH) norepinephrine-expressing cell lines were used for in vitro tracer uptake studies. After 2 h of \(^{18}\)F-LMI1195 preloading into both cell lines, effects of stimulants for storage vesicle turnover (high concentration KCl (100 mM) or reserpine treatment) were measured at 10, 20, and 30 min. \(^{131}\)I-meta-iodobenzylguanidine (\(^{131}\)I-MIBG) served as a reference. Both high concentration KCl and reserpine enhanced \(^{18}\)F-LMI1195 washout from PC12 cells, while tracer retention remained stable in the SK-N-SH cells. After 30 min of treatment, 18F-LMI1195 releasing index (percentage of tracer released from cells) from vesicle-rich PC12 cells achieved significant differences compared to cells without treatment condition. In contrast, such effect could not be observed using vesicle-poor SK-N-SH cell lines. Similar tracer kinetics after KCl or reserpine treatment were also observed using 131I-MIBG. In case of KCl exposure, Ca\(^{2+}\)-free buffer with the calcium chelator, ethylenediaminetetracetic acid (EDTA), could suppress the tracer washout from PC12 cells. This finding is consistent with the tracer release being mediated by Ca\(^{2+}\) influx resulting from membrane depolarization. Conclusions: Analogous to \(^{131}\)I-MIBG, the current in vitro tracer uptake study confirmed that \(^{131}\)F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of \(^{18}\)FLMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{ChifuHeinzeFussetal.2020,
  author    = {Chifu, Irina and Heinze, Britta and Fuss, Carmina T. and Lang, Katharina and Kroiss, Matthias and Kircher, Stefan and Ronchi, Cristina L. and Altieri, Barbara and Schirbel, Andreas and Fassnacht, Martin and Hahner, Stefanie},
  title     = {Impact of the Chemokine Receptors CXCR4 and CXCR7 on Clinical Outcome in Adrenocortical Carcinoma},
  series = {Frontiers in Endocrinology},
  volume    = {11},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2020.597878},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216494},
  year      = {2020},
  abstract  = {Chemokine receptors have a negative impact on tumor progression in several human cancers and have therefore been of interest for molecular imaging and targeted therapy. However, their clinical and prognostic significance in adrenocortical carcinoma (ACC) is unknown. The aim of this study was to evaluate the chemokine receptor profile in ACC and to analyse its association with clinicopathological characteristics and clinical outcome. A chemokine receptor profile was initially evaluated by quantitative PCR in 4 normal adrenals, 18 ACC samples and human ACC cell line NCI-H295. High expression of CXCR4 and CXCR7 in both healthy and malignant adrenal tissue and ACC cells was confirmed. In the next step, we analyzed the expression and cellular localization of CXCR4 and CXCR7 in ACC by immunohistochemistry in 187 and 84 samples, respectively. These results were correlated with clinicopathological parameters and survival outcome. We detected strong membrane expression of CXCR4 and CXCR7 in 50\% of ACC samples. Strong cytoplasmic CXCR4 staining was more frequent among samples derived from metastases compared to primaries (p=0.01) and local recurrences (p=0.04). CXCR4 membrane staining positively correlated with proliferation index Ki67 (r=0.17, p=0.028). CXCR7 membrane staining negatively correlated with Ki67 (r=-0.254, p=0.03) but positively with tumor size (r=0.3, p=0.02). No differences in progression-free or overall survival were observed between patients with strong and weak staining intensities for CXCR4 or CXCR7. Taken together, high expression of CXCR4 and CXCR7 in both local tumors and metastases suggests that some ACC patients might benefit from CXCR4/CXCR7-targeted therapy.},
  language  = {en}
}
@article{DaViaSolimandoGaritanoTrojaolaetal.2019,
  author    = {Da Vi{\`a}, Matteo Claudio and Solimando, Antonio Giovanni and Garitano-Trojaola, Andoni and Barrio, Santiago and Munawar, Umair and Strifler, Susanne and Haertle, Larissa and Rhodes, Nadine and Vogt, Cornelia and Lapa, Constantin and Beilhack, Andreas and Rasche, Leo and Einsele, Hermann and Kort{\"u}m, K. Martin},
  title     = {CIC Mutation as a Molecular Mechanism of Acquired Resistance to Combined BRAF-MEK Inhibition in Extramedullary Multiple Myeloma with Central Nervous System Involvement},
  series = {The Oncologist},
  volume    = {25},
  journal   = {The Oncologist},
  number    = {2},
  doi       = {10.1634/theoncologist.2019-0356},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219549},
  pages     = {112-118},
  year      = {2019},
  abstract  = {Combined MEK-BRAF inhibition is a well-established treatment strategy in BRAF-mutated cancer, most prominently in malignant melanoma with durable responses being achieved through this targeted therapy. However, a subset of patients face primary unresponsiveness despite presence of the activating mutation at position V600E, and others acquire resistance under treatment. Underlying resistance mechanisms are largely unknown, and diagnostic tests to predict tumor response to BRAF-MEK inhibitor treatment are unavailable. Multiple myeloma represents the second most common hematologic malignancy, and point mutations in BRAF are detectable in about 10\% of patients. Targeted inhibition has been successfully applied, with mixed responses observed in a substantial subset of patients mirroring the widespread spatial heterogeneity in this genomically complex disease. Central nervous system (CNS) involvement is an extremely rare, extramedullary form of multiple myeloma that can be diagnosed in less than 1\% of patients. It is considered an ultimate high-risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases. Here we not only describe the first patient with an extramedullary CNS relapse responding to targeted dabrafenib and trametinib treatment, we furthermore provide evidence that a point mutation within the capicua transcriptional repressor (CIC) gene mediated the acquired resistance in this patient.},
  language  = {en}
}
@article{DetomasAltieriSchloetelburgetal.2021,
  author    = {Detomas, Mario and Altieri, Barbara and Schl{\"o}telburg, Wiebke and Appenzeller, Silke and Schlaffer, Sven and Coras, Roland and Schirbel, Andreas and Wild, Vanessa and Kroiss, Matthias and Sbiera, Silviu and Fassnacht, Martin and Deutschbein, Timo},
  title     = {Case Report: Consecutive Adrenal Cushing's Syndrome and Cushing's Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations},
  series = {Frontiers in Endocrinology},
  volume    = {12},
  journal   = {Frontiers in Endocrinology},
  issn      = {1664-2392},
  doi       = {10.3389/fendo.2021.731579},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244596},
  year      = {2021},
  abstract  = {The occurrence of different subtypes of endogenous Cushing's syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing's disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the β-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.},
  language  = {en}
}
@article{DicksonEberleinLassmann2022,
  author    = {Dickson, John and Eberlein, Uta and Lassmann, Michael},
  title     = {The effect of modern PET technology and techniques on the EANM paediatric dosage card},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {6},
  issn      = {1619-7089},
  doi       = {10.1007/s00259-021-05635-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265624},
  pages     = {1964-1969},
  year      = {2022},
  abstract  = {Aim Recent advancements in PET technology have brought with it significant improvements in PET performance and image quality. In particular, the extension of the axial field of view of PET systems, and the introduction of semiconductor technology into the PET detector, initially for PET/MR, and more recently available long-field-of-view PET/CT systems (≥ 25 cm) have brought a step change improvement in the sensitivity of PET scanners. Given the requirement to limit paediatric doses, this increase in sensitivity is extremely welcome for the imaging of children and young people. This is even more relevant with PET/MR, where the lack of CT exposures brings further dose reduction benefits to this population. In this short article, we give some details around the benefits around new PET technology including PET/MR and its implications on the EANM paediatric dosage card. Material and methods Reflecting on EANM adult guidance on injected activities, and making reference to bed overlap and the concept of MBq.min bed\(^{-1}\) kg\(^{-1}\), we use published data on image quality from PET/MR systems to update the paediatric dosage card for PET/MR and extended axial field of view (≥ 25 cm) PET/CT systems. However, this communication does not cover the expansion of paediatric dosing for the half-body and total-body scanners that have recently come to market. Results In analogy to the existing EANM dosage card, new parameters for the EANM paediatric dosage card were developed (class B, baseline value: 10.7 MBq, minimum recommended activity 10 MBq). The recommended administered activities for the systems considered in this communication range from 11 MBq [\(^{18}\)F]FDG for a child with a weight of 3 kg to 149 MBq [\(^{18}\)F]FDG for a paediatric patient weight of 68 kg, assuming a scan of 3 min per bed position. The mean effective dose over all ages (1 year and older) is 2.85 mSv. Conclusion With this, recommendations for paediatric dosing are given for systems that have not been considered previously.},
  language  = {en}
}
@phdthesis{Diessl2010,
  author    = {Dießl, Stefanie},
  title     = {Implementierung und Evaluation einer integrierten E-Learning-Plattform f{\"u}r die Nuklearmedizin},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-52643},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Zum Thema „Implementierung und Evaluation einer integrierten E-Learning-Plattform f{\"u}r die Nuklearmedizin" wurde zu Beginn zun{\"a}chst auf die drei existierenden Lerntheorien - Behaviorismus, Kognitivismus und Konstruktivismus - n{\"a}her eingegangen, diese miteinander verglichen und in der Folge eine Verbindung zu computerunterst{\"u}tzten Lernprogrammen hergestellt. In Erg{\"a}nzung dazu wurde der Begriff „E-Learning" als Kernpunkt des Dissertationsthemas recherchiert und aus verschiedenen Blickwinkeln er{\"o}rtert. Um feststellen zu k{\"o}nnen, ob die Einf{\"u}hrung eines E-Learning-Angebots im Fachgebiet Nuklearmedizin f{\"u}r die Medizinstudenten des 6. Semesters „gewinnbringend" ist, wurden f{\"u}r den Kurs „Grundlagen radiologischer Verfahren" an der Julius-Maximilians-Universit{\"a}t W{\"u}rzburg 20 Patientenf{\"a}lle aus der hiesigen Klinik und Poliklinik f{\"u}r Nuklearmedizin erstellt und diese mittels Fallplayer CaseTrain f{\"u}r das Internet generiert. Im Anschluss wurden zur Qualit{\"a}tskontrolle des Projekts drei ausgew{\"a}hlte F{\"a}lle bearbeitet und evaluiert. Es wurden insgesamt 128 Beurteilungen ausgewertet, diese zeigten als wichtigstes Ergebnis, dass sich nach Einsch{\"a}tzung der Evaluierenden ihr Interesse und Wissen am bzw. im Fach Nuklearmedizin nach der Bearbeitung des E-Learning-Kurses signifikant erh{\"o}ht haben. Aussagekr{\"a}ftig ist auch die Erkenntnis, dass nahezu 100\% der Studierenden den Einsatz von computerunterst{\"u}tzten Lernmedien f{\"u}r das Humanmedizinstudium generell f{\"u}r sinnvoll erachten, nur 3\% der Befragten eine k{\"u}nftige Benutzung des Programms ablehnten und die Benotung in Bezug auf Fallinhalt und Softwarebedienung {\"u}berdurchschnittlich gut ausfiel. Aus diesem Grund erscheint es nach Ansicht der Verfasserin sinnvoll, elektronisches Lernen mit der Pr{\"a}senzlehre im Sinne des „Blended Learning" zu kombinieren. Zu diesem Zweck wird der Kurs „NUKlearn" {\"u}ber die Plattform der Virtuellen Hochschule Bayern k{\"u}nftig {\"o}ffentlich angeboten.},
  subject      = {E-learning},
  language  = {de}
}
@phdthesis{Doyle2010,
  author    = {Doyle, Patricia},
  title     = {Neubestimmung des Referenzbereiches f{\"u}r Serum-Calcitonin basal sowie nach Stimulation mit Pentagastrin bzw. Calcium bei gesunden Probanden},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51805},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Ziel: Im Mittelpunkt dieser prospektiven Studie steht die Neubestimmung eines geschlechtspezifischen Referenzbereiches f{\"u}r Calcitonin-Konzentrationen, sowohl basal als auch nach Stimulation mit Pentagastrin bzw. Calcium unter Verwendung eines vollautomatischen Assays (Analyseautomat IMMULITE®2000). Aufgrund des gew{\"a}hlten Studiendesigns ist es m{\"o}glich, die Wertigkeit des etablierten Pentagastrin-Stimulationstests im Vergleich zu einem alternativen Calcium-Stimulationstest zu beurteilen. Methodik: Insgesamt wurden 50 schilddr{\"u}sengesunde, nichtrauchende Versuchspersonen (davon 25 weiblich) im Alter von 20 bis 60 Jahren (Mittelwert: 33 Jahre) in die Studie eingeschlossen. Im Vorfeld wurde bei jedem Probanden mittels sonographischer und labortechnischer Untersuchungen (fT3, FT4, TSH, TPO-Antik{\"o}rper, TG-Antik{\"o}rper) das Vorliegen krankhafter Ver{\"a}nderungen der Schilddr{\"u}se ausgeschlossen. Um einen intraindividuellen Vergleich der intraven{\"o}sen Stimulationsverfahren zu erm{\"o}glichen, erfolgten die Stimulationsversuche unter gleichen Bedingungen (Nahrungskarenz >4h) in einem zeitlichen Abstand von mehreren Wochen. Die Anzahl der Probanden, die an beiden Versuchen teilnahmen, lag bei 42 (davon 18 Frauen). Die Durchf{\"u}hrung des Pentagastrin-Tests erfolgte nach dem in unserer Klinik etablierten Protokoll: 0,5 μg Pentagastrin/ kg K{\"o}rpergewicht Injektion innerhalb von 10 sec.. Die Dosierung des Stimulans Calcium richtete sich nach Angaben der Literatur. Die Stimulation mit Calcium wurde mit Calciumgluconatl{\"o}sung durchgef{\"u}hrt (2,5 mg Calcium/kg K{\"o}rpergewicht, mit einer Injektionsgeschwindigkeit von etwa 10ml/min). Vor der Stimulation wurde jeweils der basale Calcitoninspiegel bestimmt. Weitere Blutabnahmen erfolgten direkt im Anschluss an die Injektion sowie 2, 5 und 15 Minuten nach Injektionsende. S{\"a}mtliche Calcitoninkonzentrationen wurden mit Hilfe eines Festphasen, Enzym-markierten, Sandwich, immunometrischen Chemilunineszenz Assay (IMMULITE®2000 Calcitonin) bestimmt. Ergebnisse Bei der Betrachtung der 95. Perzentile des basalen Calcitoninspiegels zeigte sich kein deutlicher geschlechtspezifischer Unterschied (95. Perzentile: M{\"a}nner: 5,0 pg/ml vs. Frauen: 5,7 pg/ml; Mittelwert: M{\"a}nner: 2,6±1,3 pg/ml vs. Frauen 1,6±1,3 pg/ml). Bei den Stimulationsverfahren hingegen lagen die Calcitoninkonzentrationen in der Gruppe der M{\"a}nner im Vergleich zur Gruppe der Frauen jeweils signifikant h{\"o}her (Pentagastrin-Test: p=0,001; Calcium-Test: p=0,004; Mann-Whitney Test). In beiden Testverfahren wurde der Calcitonin Peak nach 2 bis 5 Minuten erreicht. Bei der Gegen{\"u}berstellung des Pentagastrin-Tests und des Calcium-Tests bewirkte letzterer den gr{\"o}ßeren Calcitoninanstieg (M{\"a}nner: p<0,001, Frauen: p<0,001). Im Einzelnen lag der Wert der 95. Perzentile - zum Zeitpunkt der 2-Minuten-Messung - f{\"u}r M{\"a}nner im Pentagastrin-Test bei 37,8 pg/ml (Frauen: 26,2 pg/ml) und im Calcium Test bei 95,4 pg/ml (Frauen: 90,2 pg/ml). Die Daten zeigten keinen Anhalt f{\"u}r einen Einfluss von Alter oder Gewicht. Schlussfolgerung Die mit Hilfe eines verbreiteten Analyseautomaten ermittelten geschlechtsspezifischen Referenzbereiche f{\"u}r Calcitonin liegen unterhalb der bisherigen f{\"u}r andere Messverfahren erarbeiteten Angaben. Bei einem schilddr{\"u}sengesunden Kollektiv bewirkte die Stimulation mit Calcium im Vergleich zu Pentagastrin einen st{\"a}rkeren Calcitoninanstieg.},
  subject      = {Calcitonin},
  language  = {de}
}
@article{DrozdSaenkoBrenneretal.2015,
  author    = {Drozd, Valentina M. and Saenko, Vladimir A. and Brenner, Alina V. and Drozdovitch, Vladimir and Pashkevich, Vasilii I. and Kudelsky, Anatoliy V. and Demidchik, Yuri E. and Branovan, Igor and Shiglik, Nikolay},
  title     = {Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0137226},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141863},
  pages     = {e0137226},
  year      = {2015},
  abstract  = {One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (I-131) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the I-131-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.},
  language  = {en}
}
@article{DrozdSaenkoBranovanetal.2021,
  author    = {Drozd, Valentina and Saenko, Vladimir and Branovan, Daniel I. and Brown, Kate and Yamashita, Shunichi and Reiners, Christoph},
  title     = {A search for causes of rising incidence of differentiated thyroid cancer in children and adolescents after Chernobyl and Fukushima: comparison of the clinical features and their relevance for treatment and prognosis},
  series = {International Journal of Environmental Research and Public Health},
  volume    = {18},
  journal   = {International Journal of Environmental Research and Public Health},
  number    = {7},
  issn      = {1660-4601},
  doi       = {10.3390/ijerph18073444},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234247},
  year      = {2021},
  abstract  = {The incidence of differentiated thyroid cancer (DTC) is steadily increasing globally. Epidemiologists usually explain this global upsurge as the result of new diagnostic modalities, screening and overdiagnosis as well as results of lifestyle changes including obesity and comorbidity. However, there is evidence that there is a real increase of DTC incidence worldwide in all age groups. Here, we review studies on pediatric DTC after nuclear accidents in Belarus after Chernobyl and Japan after Fukushima as compared to cohorts without radiation exposure of those two countries. According to the Chernobyl data, radiation-induced DTC may be characterized by a lag time of 4-5 years until detection, a higher incidence in boys, in children of youngest age, extrathyroidal extension and distant metastases. Radiation doses to the thyroid were considerably lower by appr. two orders of magnitude in children and adolescents exposed to Fukushima as compared to Chernobyl. In DTC patients detected after Fukushima by population-based screening, most of those characteristics were not reported, which can be taken as proof against the hypothesis, that radiation is the (main) cause of those tumors. However, roughly 80\% of the Fukushima cases presented with tumor stages higher than microcarcinomas pT1a and 80\% with lymph node metastases pN1. Mortality rates in pediatric DTC patients are generally very low, even at higher tumor stages. However, those cases considered to be clinically relevant should be followed-up carefully after treatment because of the risk of recurrencies which is expected to be not negligible. Considering that thyroid doses from the Fukushima accident were quite small, it makes sense to assess the role of other environmental and lifestyle-related factors in thyroid carcinogenesis. Well-designed studies with assessment of radiation doses from medical procedures and exposure to confounders/modifiers from the environment as e.g., nitrate are required to quantify their combined effect on thyroid cancer risk.},
  language  = {en}
}
@article{EberleinBroeerVandevoordeetal.2011,
  author    = {Eberlein, Uta and Br{\"o}er, J{\"o}rn Hendrik and Vandevoorde, Charlot and Santos, Paula and Bardi{\`e}s, Manuel and Bacher, Klaus and Nosske, Dietmar and Lassmann, Michael},
  title     = {Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine - a review},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {38},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {12},
  doi       = {10.1007/s00259-011-1904-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133846},
  pages     = {2269-2281},
  year      = {2011},
  abstract  = {Purpose The impact on patients' health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE.NET (www.​peddose.​net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.​ncbi.​nlm.​nih.​gov/​pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained.},
  language  = {en}
}
@article{EberleinPeperFernandezetal.2015,
  author    = {Eberlein, Uta and Peper, Michel and Fern{\´a}ndez, Maria and Lassmann, Michael and Scherthan, Harry},
  title     = {Calibration of the \(\gamma\)-H2AX DNA double strand break focus assay for internal radiation exposure of blood lymphocytes},
  series = {PLoS ONE},
  volume    = {10},
  journal   = {PLoS ONE},
  number    = {4},
  doi       = {10.1371/journal.pone.0123174},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148697},
  pages     = {e0123174},
  year      = {2015},
  abstract  = {DNA double strand break (DSB) formation induced by ionizing radiation exposure is indicated by the DSB biomarkers \(\gamma\)-H2AX and 53BP1. Knowledge about DSB foci formation in-vitro after internal irradiation of whole blood samples with radionuclides in solution will help us to gain detailed insights about dose-response relationships in patients after molecular radiotherapy (MRT). Therefore, we studied the induction of radiation-induced co-localizing \(\gamma\)-H2AX and 53BP1 foci as surrogate markers for DSBs in-vitro, and correlated the obtained foci per cell values with the in-vitro absorbed doses to the blood for the two most frequently used radionuclides in MRT (I-131 and Lu-177). This approach led to an in-vitro calibration curve. Overall, 55 blood samples of three healthy volunteers were analyzed. For each experiment several vials containing a mixture of whole blood and radioactive solutions with different concentrations of isotonic NaCl-diluted radionuclides with known activities were prepared. Leukocytes were recovered by density centrifugation after incubation and constant blending for 1 h at 37°C. After ethanol fixation they were subjected to two-color immunofluorescence staining and the average frequencies of the co-localizing \(\gamma\)-H2AX and 53BP1 foci/nucleus were determined using a fluorescence microscope equipped with a red/green double band pass filter. The exact activity was determined in parallel in each blood sample by calibrated germanium detector measurements. The absorbed dose rates to the blood per nuclear disintegrations occurring in 1 ml of blood were calculated for both isotopes by a Monte Carlo simulation. The measured blood doses in our samples ranged from 6 to 95 mGy. A linear relationship was found between the number of DSB-marking foci/nucleus and the absorbed dose to the blood for both radionuclides studied. There were only minor nuclide-specific intra-and inter-subject deviations.},
  language  = {en}
}
@article{EilsbergerKreisslReinersetal.2023,
  author    = {Eilsberger, Friederike and Kreissl, Michael C. and Reiners, Christoph and Holzgreve, Adrien and Luster, Markus and Pfestroff, Andreas},
  title     = {Application of the American Thyroid Association risk assessment in patients with differentiated thyroid carcinoma in a German population},
  series = {Biomedicines},
  volume    = {11},
  journal   = {Biomedicines},
  number    = {3},
  issn      = {2227-9059},
  doi       = {10.3390/biomedicines11030911},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311226},
  year      = {2023},
  abstract  = {Background: The American Thyroid Association (ATA) uses criteria to assess the risk for persistent disease in differentiated thyroid carcinoma (DTC) after radioiodine therapy (RAI). There are no data available showing that this classification can be adopted unadjusted by Germany. Aim: The aim of our study is to investigate whether the ATA classification can be applied to a German population for short-term prognosis. Furthermore, we investigated the influence of an age cutoff value. Methods: We retrospectively analyzed 121 patients who were referred to our tertiary referral center. Patients were classified into risk categories, and the therapy response was determined according to ATA. Results: A total of 73/83 (88\%) ATA low-risk patients and 12/19 (63\%) intermediate-risk patients showed an excellent response; 2/19 (11\%) high-risk patients had a biochemical, and 6 (31\%) had a structural incomplete response. Of all 39 patients ≥55 years, 84\% had an excellent response. Using a cut off of 50 years, 50/62 (81\%) of the older patients showed an excellent response. Conclusion: The ATA risk classification is able to estimate the response to RAI therapy in a German population. A shift from 55 to 50 years as an age cutoff value does not result in any relevant change in the treatment response.},
  language  = {en}
}
@article{EisslerWernerAriasLozaetal.2021,
  author    = {Eissler, Cristoph and Werner, Rudolf A. and Arias-Loza, Paula and Nose, Naoko and Chen, Xinyu and Pomper, Martin G. and Rowe, Steven P. and Lapa, Constantin and Buck, Andreas K. and Higuchi, Takahiro},
  title     = {The number of frames on ECG-gated \(^{18}\)F-FDG small animal PET has a significant impact on LV systolic and diastolic functional parameters},
  series = {Molecular Imaging},
  volume    = {2021},
  journal   = {Molecular Imaging},
  doi       = {10.1155/2021/4629459},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265778},
  year      = {2021},
  abstract  = {Objectives. This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. Methods. \(^{18}\)F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed. Results. Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 \& PLUSMN; 57.7 mu l*, 380.8 \& PLUSMN; 57.2 mu l*, 398.0 \& PLUSMN; 63.1 mu l*, and 444.8 \& PLUSMN; 75.3 mu l at 4, 8, 12, and 16 frames, respectively; *P < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed (P < 0.005), but not for 4, 8, and 12 frames. Conclusions. Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.},
  language  = {en}
}
@phdthesis{Eissler2021,
  author    = {Eißler, Christoph Marcel},
  title     = {Assessment of the left ventricular systolic and diastolic function in rats using electrocardiogram-gated cardiac positron emission tomography},
  doi       = {10.25972/OPUS-21976},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219765},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {DD is a cardiac disturbance, which has gained increasing importance in recent years due to its important role in different cardiac disease and cardiomyopathies including ischemic cardiomyopathy, arterial hypertension and diabetic cardiomyopathy. ECG-gated 18F-FDG PET is an imaging technique, that can distinguish between districts of myocardial viability and myocardial scars and further provides information of great interest on the efficacy of experimental approaches designed to improve the cardiac function and/or myocardial metabolism in experimental small animal models. However, ECG-gated 18F-FDG PET is a technique whose feasibility in the assessment of the LV diastolic function in small animals has not been a subject of study. In this thesis, the ability of the ECG-gated 18F-FDG PET for the assessment of both the systolic and diastolic function in eight control rats and in seven ZDF rats, which are an experimental animal model mimicking T2DM conditions and diabetic related complications in humans including DCM, has been investigated The ECG-gated 18F-FDG PET imaging was performed under hyperinsulinemic-euglycemic clamping and the data were stored in list mode files and retrospectively reconstructed. The systolic and diastolic parameters were achieved from the time/volume and the time/filling curve calculated from the software HFV. Additionally, the influence of the number of gates per cardiac cycle on the LV volumes and function parameters has been studied. Hyperinsulinemic-euglycemic clamp procedure and blood glucose measurement did confirm the development of a manifest diabetes in the ZDF rats at the timepoint of the experiments. Regarding the systolic parameters, no significant difference could be detected between the ZDF and ZL rats. The values for the CO were similar in both groups, which demonstrates a similar LV systolic function in the ZDF and the ZL rats at the age of 13 weeks. Values for the systolic parameters are in good line with previous PET, MRI and cardiac catheterization-based studies in diabetic rats. The main finding of this study was that by using in vivo ECG-gated 18F-FDG PET and the software HFV, reliable diastolic parameters could be calculated. Moreover, it was possible to detect the presence of a mild impaired diastolic filling in the ZDF rats in absence of any systolic alteration. This impaired diastolic function in an early stage of diabetes could also be detected by other investigators, who used echocardiography or cardiac catheterization. Therefore, this is the first study showing, that the assessment of the diastolic function in rats can be carried out by ECG-gated 18F-FDG PET imaging. In conclusion, additionally to calculating LV volumes and LV EF, ECG-gated 18F-FDG PET can evaluate the diastolic function of healthy and diabetic rats and is able to detect a DD in ZDF rats.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{FecherHofmannBucketal.2016,
  author    = {Fecher, David and Hofmann, Elisabeth and Buck, Andreas and Bundschuh, Ralph and Nietzer, Sarah and Dandekar, Gudrun and Walles, Thorsten and Walles, Heike and L{\"u}ckerath, Katharina and Steinke, Maria},
  title     = {Human Organotypic Lung Tumor Models: Suitable For Preclinical \(^{18}\)F-FDG PET-Imaging},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0160282},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179678},
  year      = {2016},
  abstract  = {Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose positron emission tomography (FDG-PET) these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.},
  language  = {en}
}
@article{FroehlichSerflingHiguchietal.2021,
  author    = {Fr{\"o}hlich, Matthias and Serfling, Sebastian and Higuchi, Takahiro and Pomper, Martin G. and Rowe, Steven P. and Schmalzing, Marc and Tony, Hans-Peter and Gernert, Michael and Strunz, Patrick-Pascal and Portegys, Jan and Schwaneck, Eva-Christina and Gadeholt, Ottar and Weich, Alexander and Buck, Andreas K. and Bley, Thorsten A. and Guggenberger, Konstanze V. and Werner, Rudolf A.},
  title     = {Whole-Body [\(^{18}\)F]FDG PET/CT Can Alter Diagnosis in Patients with Suspected Rheumatic Disease},
  series = {Diagnostics},
  volume    = {11},
  journal   = {Diagnostics},
  number    = {11},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics11112073},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250227},
  year      = {2021},
  abstract  = {The 2-deoxy-d-[\(^{18}\)F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is widely utilized to assess the vascular and articular inflammatory burden of patients with a suspected diagnosis of rheumatic disease. We aimed to elucidate the impact of [\(^{18}\)F]FDG PET/CT on change in initially suspected diagnosis in patients at the time of the scan. Thirty-four patients, who had undergone [\(^{18}\)F]FDG PET/CT, were enrolled and the initially suspected diagnosis prior to [18F]FDG PET/CT was compared to the final diagnosis. In addition, a semi-quantitative analysis including vessel wall-to-liver (VLR) and joint-to-liver (JLR) ratios was also conducted. Prior to [\(^{18}\)F]FDG PET/CT, 22/34 (64.7\%) of patients did not have an established diagnosis, whereas in 7/34 (20.6\%), polymyalgia rheumatica (PMR) was suspected, and in 5/34 (14.7\%), giant cell arteritis (GCA) was suspected by the referring rheumatologists. After [\(^{18}\)F]FDG PET/CT, the diagnosis was GCA in 19/34 (55.9\%), combined GCA and PMR (GCA + PMR) in 9/34 (26.5\%) and PMR in the remaining 6/34 (17.6\%). As such, [\(^{18}\)F]FDG PET/CT altered suspected diagnosis in 28/34 (82.4\%), including in all unclear cases. VLR of patients whose final diagnosis was GCA tended to be significantly higher when compared to VLR in PMR (GCA, 1.01 ± 0.08 (95\%CI, 0.95-1.1) vs. PMR, 0.92 ± 0.1 (95\%CI, 0.85-0.99), p = 0.07), but not when compared to PMR + GCA (1.04 ± 0.14 (95\%CI, 0.95-1.13), p = 1). JLR of individuals finally diagnosed with PMR (0.94 ± 0.16, (95\%CI, 0.83-1.06)), however, was significantly increased relative to JLR in GCA (0.58 ± 0.04 (95\%CI, 0.55-0.61)) and GCA + PMR (0.64 ± 0.09 (95\%CI, 0.57-0.71); p < 0.0001, respectively). In individuals with a suspected diagnosis of rheumatic disease, an inflammatory-directed [\(^{18}\)F]FDG PET/CT can alter diagnosis in the majority of the cases, particularly in subjects who were referred because of diagnostic uncertainty. Semi-quantitative assessment may be helpful in establishing a final diagnosis of PMR, supporting the notion that a quantitative whole-body read-out may be useful in unclear cases.},
  language  = {en}
}
@article{GargWernerChungetal.2022,
  author    = {Garg, Tushar and Werner, Rudolf A. and Chung, Hyun Woo and Khatri, Wajahat and Pienta, Kenneth J. and Pomper, Martin G. and Gorin, Michael A. and Saad, Elie and Rowe, Steven P.},
  title     = {Association of true positivity with serum prostate-specific antigen levels and other clinical factors in indeterminate PSMA-RADS-3A lesions identified on \(^{18}\)F-DCFPyL PET/CT scans},
  series = {Tomography},
  volume    = {8},
  journal   = {Tomography},
  number    = {6},
  issn      = {2379-139X},
  doi       = {10.3390/tomography8060220},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290510},
  pages     = {2639 -- 2647},
  year      = {2022},
  abstract  = {The use of prostate-specific membrane antigen targeted PET imaging for the evaluation of prostate cancer has increased significantly in the last couple of decades. When evaluating these imaging findings based on the PSMA reporting and data system version 1.0, which categorize lesions based on their likelihood of prostate cancer involvement, PSMA-RADS-3A lesions are commonly seen, which are indeterminate for the presence of disease. A total of 28 patients with 171 PSMA-RADS-3A lesions on \(^{18}\)F-DCFPyL PET/CT scans from June 2016 to May 2017 who had follow-up cross-sectional imaging over time were included in this study. The PSA levels of patients with PSMA-RADS-3A lesions were categorized into four groups, 0-0.2, 0.2-1, 1-2, and >2 ng/mL. The pre-operative Gleason score of these patients was categorized into two groups, Gleason score < 7 or ≥7. The median age for these patients was 72.5 years (range 59-81). The median PSA value for patients with positive lesions was significantly higher than those with negative lesions (5.8 ng/mL vs. 0.2 ng/mL, p < 0.0001). The lesion positivity rate was significantly higher in patients with PSA > 1 ng/mL (18.2\% vs. 81.9\%, p < 0.001). On ROC analysis, the highest classification accuracy was seen at PSA ≥ 0.6 ng/mL of 80.12\% (95\% CI = 73.69-86.16\%), and the area under the curve was 71.32\% (95\% CI = 61.9-80.7\%, p < 0.0001). A total of 96.4\% (108/112) of patients with positive lesions and 86.4\% (51/59) of patients with negative lesions had a PSMA-RADS-4/5 lymph node on the initial \(^{18}\)F-DCFPyL PET/CT scan (p = 0.02). In patients with a Gleason score ≥ 7, the presence of positive PSMA-RADS-3A lesions was higher, compared to negative PSMA-RADS-3A lesions (p = 0.049). Higher PSA levels in patients with PSMA-RADS-3A lesions can point towards the presence of true positivity. PSA levels may be considered in deciding whether to call an indeterminate lesion on PSMA PET.},
  language  = {en}
}
@article{GentzschChenSpatzetal.2021,
  author    = {Gentzsch, Christian and Chen, Xinyu and Spatz, Philipp and Košak, Urban and Knez, Damijan and Nose, Naoko and Gobec, Stanislav and Higuchi, Takahiro and Decker, Michael},
  title     = {Synthesis and Initial Characterization of a Reversible, Selective \(^{18}\)F-Labeled Radiotracer for Human Butyrylcholinesterase},
  series = {Molecular Imaging and Biology},
  volume    = {23},
  journal   = {Molecular Imaging and Biology},
  number    = {4},
  issn      = {1860-2002},
  doi       = {10.1007/s11307-021-01584-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269870},
  pages     = {505-515},
  year      = {2021},
  abstract  = {Purpose A neuropathological hallmark of Alzheimer's disease (AD) is the presence of amyloid-β (Aβ) plaques in the brain, which are observed in a significant number of cognitively normal, older adults as well. In AD, butyrylcholinesterase (BChE) becomes associated with A\(_{β}\) aggregates, making it a promising target for imaging probes to support diagnosis of AD. In this study, we present the synthesis, radiochemistry, in vitro and preliminary ex and in vivo investigations of a selective, reversible BChE inhibitor as PET-tracer for evaluation as an AD diagnostic. Procedures Radiolabeling of the inhibitor was achieved by fluorination of a respective tosylated precursor using K[\(^{18}\)F]. IC\(_{50}\) values of the fluorinated compound were obtained in a colorimetric assay using recombinant, human (h) BChE. Dissociation constants were determined by measuring hBChE activity in the presence of different concentrations of inhibitor. Results Radiofluorination of the tosylate precursor gave the desired radiotracer in an average radiochemical yield of 20 ± 3 \%. Identity and > 95.5 \% radiochemical purity were confirmed by HPLC and TLC autoradiography. The inhibitory potency determined in Ellman's assay gave an IC\(_{50}\) value of 118.3 ± 19.6 nM. Dissociation constants measured in kinetic experiments revealed lower affinity of the inhibitor for binding to the acylated enzyme (K2 = 68.0 nM) in comparison to the free enzyme (K\(_{1}\) = 32.9 nM). Conclusions The reversibly acting, selective radiotracer is synthetically easily accessible and retains promising activity and binding potential on hBChE. Radiosynthesis with \(^{18}\)F labeling of tosylates was feasible in a reasonable time frame and good radiochemical yield.},
  language  = {en}
}
@article{GentzschHoffmannOhshimaetal.2021,
  author    = {Gentzsch, Christian and Hoffmann, Matthias and Ohshima, Yasuhiro and Nose, Naoko and Chen, Xinyu and Higuchi, Takahiro and Decker, Michael},
  title     = {Synthesis and Initial Characterization of a Selective, Pseudo-irreversible Inhibitor of Human Butyrylcholinesterase as PET Tracer},
  series = {ChemMedChem},
  volume    = {16},
  journal   = {ChemMedChem},
  number    = {9},
  doi       = {10.1002/cmdc.202000942},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239904},
  pages     = {1427 -- 1437},
  year      = {2021},
  abstract  = {The enzyme butyrylcholinesterase (BChE) represents a promising target for imaging probes to potentially enable early diagnosis of neurodegenerative diseases like Alzheimer's disease (AD) and to monitor disease progression in some forms of cancer. In this study, we present the design, facile synthesis, in vitro and preliminary ex vivo and in vivo evaluation of a morpholine-based, selective inhibitor of human BChE as a positron emission tomography (PET) tracer with a pseudo-irreversible binding mode. We demonstrate a novel protecting group strategy for 18F radiolabeling of carbamate precursors and show that the inhibitory potency as well as kinetic properties of our unlabeled reference compound were retained in comparison to the parent compound. In particular, the prolonged duration of enzyme inhibition of such a morpholinocarbamate motivated us to design a PET tracer, possibly enabling a precise mapping of BChE distribution.},
  language  = {en}
}
@article{GieselKratochwilSchlittenhardtetal.2021,
  author    = {Giesel, Frederik L. and Kratochwil, Clemens and Schlittenhardt, Joel and Dendl, Katharina and Eiber, Matthias and Staudinger, Fabian and Kessler, Lukas and Fendler, Wolfgang P. and Lindner, Thomas and Koerber, Stefan A. and Cardinale, Jens and Sennung, David and Roehrich, Manuel and Debus, Juergen and Sathekge, Mike and Haberkorn, Uwe and Calais, Jeremie and Serfling, Sebastian and Buck, Andreas L.},
  title     = {Head-to-head intra-individual comparison of biodistribution and tumor uptake of \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG PET/CT in cancer patients},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {48},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {13},
  issn      = {1619-7070},
  doi       = {10.1007/s00259-021-05307-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307252},
  pages     = {4377-4385},
  year      = {2021},
  abstract  = {Purpose FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of \(^{68}\)Ga-FAPI versus standard-of-care \(^{18}\)F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. Material and Methods This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). Results A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. \(^{68}\)Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for \(^{68}\)Ga-FAPI than \(^{18}\)F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, \(^{68}\)Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases. Conclusion Quantitative tumor uptake is comparable between \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for \(^{68}\)Ga-FAPI. Thus, \(^{68}\)Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological \(^{18}\)F-FDG uptake.},
  language  = {en}
}
@article{GrafLiHerrmannetal.2014,
  author    = {Graf, Nicolas and Li, Zhoulei and Herrmann, Ken and Weh, Daniel and Aichler, Michaela and Slawska, Jolanta and Walch, Axel and Peschel, Christian and Schwaiger, Markus and Buck, Andreas K. and Dechow, Tobias and Keller, Ulrich},
  title     = {Positron emission tomographic monitoring of dual phosphatidylinositol-3-kinase and mTOR inhibition in anaplastic large cell lymphoma},
  series = {Oncotargets and Therapy},
  volume    = {7},
  journal   = {Oncotargets and Therapy},
  doi       = {10.2147/OTT.S59314},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117915},
  pages     = {789-798},
  year      = {2014},
  abstract  = {Background: Dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibition offers an attractive therapeutic strategy in anaplastic large cell lymphoma depending on oncogenic nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) signaling. We tested the efficacy of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in two anaplastic large cell lymphoma cell lines in vitro and in vivo and performed an early response evaluation with positron emission tomography (PET) imaging using the standard tracer, 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) and the thymidine analog, 3'-deoxy-3'-[F-18] fluorothymidine (FLT). Methods: The biological effects of BGT226 were determined in vitro in the NPM-ALK positive cell lines SU-DHL-1 and Karpas299 by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, propidium iodide staining, and biochemical analysis of PI3K and mTOR downstream signaling. FDG-PET and FLT-PET were performed in immunodeficient mice bearing either SU-DHL-1 or Karpas299 xenografts at baseline and 7 days after initiation of treatment with BGT226. Lymphomas were removed for immunohistochemical analysis of proliferation and apoptosis to correlate PET findings with in vivo treatment effects. Results: SU-DHL-1 cells showed sensitivity to BGT226 in vitro, with cell cycle arrest in G0/G1 phase and an IC50 in the low nanomolar range, in contrast with Karpas299 cells, which were mainly resistant to BGT226. In vivo, both FDG-PET and FLT-PET discriminated sensitive from resistant lymphoma, as indicated by a significant reduction of tumor-to-background ratios on day 7 in treated SU-DHL-1 lymphoma-bearing animals compared with the control group, but not in animals with Karpas299 xenografts. Imaging results correlated with a marked decrease in the proliferation marker Ki67, and a slight increase in the apoptotic marker, cleaved caspase 3, as revealed by immunostaining of explanted lymphoma tissue. Conclusion: Dual PI3K/mTOR inhibition using BGT226 is effective in ALK-positive anaplastic large cell lymphoma and can be monitored with both FDG-PET and FLT-PET early on in the course of therapy.},
  language  = {en}
}
@article{GramGenslerAlbertovaetal.2022,
  author    = {Gram, Maximilian and Gensler, Daniel and Albertova, Petra and Gutjahr, Fabian Tobias and Lau, Kolja and Arias-Loza, Paula-Anahi and Jakob, Peter Michael and Nordbeck, Peter},
  title     = {Quantification correction for free-breathing myocardial T1ρ mapping in mice using a recursively derived description of a T\(_{1p}\)\(^{*}\) relaxation pathway},
  series = {Journal of Cardiovascular Magnetic Resonance},
  volume    = {24},
  journal   = {Journal of Cardiovascular Magnetic Resonance},
  number    = {1},
  doi       = {10.1186/s12968-022-00864-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300491},
  year      = {2022},
  abstract  = {Background Fast and accurate T1ρ mapping in myocardium is still a major challenge, particularly in small animal models. The complex sequence design owing to electrocardiogram and respiratory gating leads to quantification errors in in vivo experiments, due to variations of the T\(_{1p}\) relaxation pathway. In this study, we present an improved quantification method for T\(_{1p}\) using a newly derived formalism of a T\(_{1p}\)\(^{*}\) relaxation pathway. Methods The new signal equation was derived by solving a recursion problem for spin-lock prepared fast gradient echo readouts. Based on Bloch simulations, we compared quantification errors using the common monoexponential model and our corrected model. The method was validated in phantom experiments and tested in vivo for myocardial T\(_{1p}\) mapping in mice. Here, the impact of the breath dependent spin recovery time T\(_{rec}\) on the quantification results was examined in detail. Results Simulations indicate that a correction is necessary, since systematically underestimated values are measured under in vivo conditions. In the phantom study, the mean quantification error could be reduced from - 7.4\% to - 0.97\%. In vivo, a correlation of uncorrected T\(_{1p}\) with the respiratory cycle was observed. Using the newly derived correction method, this correlation was significantly reduced from r = 0.708 (p < 0.001) to r = 0.204 and the standard deviation of left ventricular T\(_{1p}\) values in different animals was reduced by at least 39\%. Conclusion The suggested quantification formalism enables fast and precise myocardial T\(_{1p}\) quantification for small animals during free breathing and can improve the comparability of study results. Our new technique offers a reasonable tool for assessing myocardial diseases, since pathologies that cause a change in heart or breathing rates do not lead to systematic misinterpretations. Besides, the derived signal equation can be used for sequence optimization or for subsequent correction of prior study results.},
  language  = {en}
}
@article{GramGenslerWinteretal.2022,
  author    = {Gram, Maximilian and Gensler, Daniel and Winter, Patrick and Seethaler, Michael and Arias-Loza, Paula Anahi and Oberberger, Johannes and Jakob, Peter Michael and Nordbeck, Peter},
  title     = {Fast myocardial T\(_{1P}\) mapping in mice using k-space weighted image contrast and a Bloch simulation-optimized radial sampling pattern},
  series = {Magnetic Resonance Materials in Physics, Biology and Medicine},
  volume    = {35},
  journal   = {Magnetic Resonance Materials in Physics, Biology and Medicine},
  number    = {2},
  issn      = {1352-8661},
  doi       = {10.1007/s10334-021-00951-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268903},
  pages     = {325-340},
  year      = {2022},
  abstract  = {Purpose T\(_{1P}\) dispersion quantification can potentially be used as a cardiac magnetic resonance index for sensitive detection of myocardial fibrosis without the need of contrast agents. However, dispersion quantification is still a major challenge, because T\(_{1P}\) mapping for different spin lock amplitudes is a very time consuming process. This study aims to develop a fast and accurate T\(_{1P}\) mapping sequence, which paves the way to cardiac T1ρ dispersion quantification within the limited measurement time of an in vivo study in small animals. Methods A radial spin lock sequence was developed using a Bloch simulation-optimized sampling pattern and a view-sharing method for image reconstruction. For validation, phantom measurements with a conventional sampling pattern and a gold standard sequence were compared to examine T\(_{1P}\) quantification accuracy. The in vivo validation of T\(_{1P}\) mapping was performed in N = 10 mice and in a reproduction study in a single animal, in which ten maps were acquired in direct succession. Finally, the feasibility of myocardial dispersion quantification was tested in one animal. Results The Bloch simulation-based sampling shows considerably higher image quality as well as improved T\(_{1P}\) quantification accuracy (+ 56\%) and precision (+ 49\%) compared to conventional sampling. Compared to the gold standard sequence, a mean deviation of - 0.46 ± 1.84\% was observed. The in vivo measurements proved high reproducibility of myocardial T\(_{1P}\) mapping. The mean T\(_{1P}\) in the left ventricle was 39.5 ± 1.2 ms for different animals and the maximum deviation was 2.1\% in the successive measurements. The myocardial T\(_{1P}\) dispersion slope, which was measured for the first time in one animal, could be determined to be 4.76 ± 0.23 ms/kHz. Conclusion This new and fast T\(_{1P}\) quantification technique enables high-resolution myocardial T\(_{1P}\) mapping and even dispersion quantification within the limited time of an in vivo study and could, therefore, be a reliable tool for improved tissue characterization.},
  language  = {en}
}