@article{WernerSolnesJavadietal.2018,
  author    = {Werner, Rudolf and Solnes, Lilja and Javadi, Mehrbod and Weich, Alexander and Gorin, Michael and Pienta, Kenneth and Higuchi, Takahiro and Buck, Andreas and Pomper, Martin and Rowe, Steven and Lapa, Constantin},
  title     = {SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.117.206631},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161298},
  year      = {2018},
  abstract  = {Reliable standards and criteria for somatostatin receptor (SSTR) positron emission tomography (PET) are still lacking. We herein propose a structured reporting system on a 5-point scale for SSTR-PET imaging, titled SSTR-RADS version 1.0, which might serve as a standardized assessment for both diagnosis and treatment planning in neuroendocrine tumors (NET). SSTR-RADS could guide the imaging specialist in interpreting SSTR-PET scans, facilitate communication with the referring clinician so that appropriate work-up for equivocal findings is pursued, and serve as a reliable tool for patient selection for planned Peptide Receptor Radionuclide Therapy.},
  subject      = {Standardisierung},
  language  = {en}
}
@phdthesis{Hueller2009,
  author    = {H{\"u}ller, Mareike},
  title     = {Stellenwert der basalen im Vergleich zur Pentagastrin-stimulierten Kalzitoninbestimmung in der Nachsorge des C-Zellkarzinoms},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-37292},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {Der spezifischste und sensitivste biochemische Tumormarker in der Diagnostik und Verlaufskontrolle des MTC ist Kalzitonin. Der hCT-Spiegel sollte nach totaler Thyreoidektomie nicht mehr messbar sein. Ein messbares hCT weist nach Therapie auf ein Rezidiv oder eine Metastasierung hin. Die hCT-Sekretion kann durch Gastrin stimuliert werden, was beim Pentagastrin-Stimulationstest genutzt wird. Im Rahmen dieser Arbeit wurde untersucht, welchen Stellenwert die Bestimmung des basalen Kalzitonin im Vergleich zum Pentagastrin-stimulierten hCT in der Nachsorge des MTC einnimmt. Hierzu wurden 129 Pentagastrintests von MTC-Patienten der Klinik und Poliklinik f{\"u}r Nuklearmedizin der Universit{\"a}t W{\"u}rzburg retrospektiv ausgewertet. Bei sechs Prozent der Patienten fand sich nach anf{\"a}nglicher biochemischer Remission ein hCT-Anstieg. Die im Pentagastrintest stimulierten hCT-Werte zeigten den Anstieg fr{\"u}her an als die lediglich basal gemessenen Werte. Das Ergebnis dieser Arbeit l{\"a}sst den Schluss zu, dass der Pentagastrintest weiterhin ein wichtiger Bestandteil in der Nachsorge von Patienten mit MTC ist, da die stimulierten hCT-Werte im Einzelfall eine noch subklinische residuelle Erkrankung, Metastasierung oder ein Rezidiv fr{\"u}hzeitig detektieren.},
  subject      = {Calcitonin},
  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{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{WernerSayehliHaenscheidetal.2023,
  author    = {Werner, Rudolf A. and Sayehli, Cyrus and H{\"a}nscheid, Heribert and Higuchi, Takahiro and Serfling, Sebastian E. and Fassnacht, Martin and Goebeler, Maria-Elisabeth and Buck, Andreas K. and Kroiss, Matthias},
  title     = {Successful combination of selpercatinib and radioiodine after pretherapeutic dose estimation in RET-altered thyroid carcinoma},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {50},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {6},
  doi       = {10.1007/s00259-022-06061-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324435},
  pages     = {1833-1834},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@phdthesis{Schneider2014,
  author    = {Schneider, Magdalena},
  title     = {Synthese, Radiomarkierung und biochemische sowie pr{\"a}klinische Evaluierung neuer Aminopeptidase N- und Fibroblasten-Aktivierungs-Protein alpha- affiner Verbindungen f{\"u}r die molekulare Bildgebung mittels Positronen-Emissions-Tomographie},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-102562},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Nach einem Myokardinfarkt setzen Wundheilungsprozesse ein, um die Durchblutung wieder herzustellen und nekrotisches Muskelgewebe durch Narbengewebe zu ersetzen. Die Einsprossung neuer Kapillaren vom bestehenden Gef{\"a}ßnetz aus wird als Angiogenese bezeichnet. Das dabei vermehrt exprimierte proteolytische Enzym Aminopeptidase N (APN) spielt eine entscheidende Rolle bei der Einsprossung von Endothelzellen. Beim kardialen Remodeling werden abgestorbene Myozyten mithilfe der Einwanderung von Fibroblasten durch Binde- oder St{\"u}tzgewebe ersetzt, dabei {\"u}bernimmt das Fibroblasten-Aktivierungs-Protein alpha (FAP) Aufgaben bei der Proliferation und Fortbewegung von Fibroblasten. Durch ihre erh{\"o}hte Expression bei den Wundheilungs- und Remodelingprozessen nach einem Herzinfarkt stellen die Metalloprotease APN und die Serinprotease FAP molekulare Targets f{\"u}r die Diagnostik und Therapie dar. Als Diagnosemethode besonders geeignet ist die Positronen-Emissions-Tomographie (PET), die es erm{\"o}glicht, biochemische Prozesse in Echtzeit im zu untersuchenden Organismus zu visualisieren und zu quantifizieren. Eine als Radiopharmakon oder Tracer bezeichnete biochemische Sonde kann im Falle eines Enzyms dessen radioaktiv markiertes Substrat oder ein Inhibitor sein. Ziel dieser Arbeit war es, spezifische APN- und FAP-affine Tracer f{\"u}r die nicht-invasive Untersuchung der APN- und FAP-Expression mittels PET zu entwickeln und dadurch die Rolle von APN und FAP bei Remodelingprozessen nach Myokardinfarkt besser verstehen bzw. kl{\"a}ren zu k{\"o}nnen. Um die Protease APN mittels PET zu untersuchen, wurden die f{\"u}r APN affine Verbindung NOTA-NGR (Komplexbildner + cyclisches Peptid inkl. Asparagin-Glycin-Arginin) mit dem Positronen-emittierenden Nuklid Gallium-68 (68Ga) markiert. Das Potential von 68Ga-NOTA-NGR als PET-Tracer wurde in vivo am Infarktmodell mittels Kleintier-PET untersucht und mit 68Ga-NOTA-RGD, einem zur Visualisierung des neo-angiogenetischen alphavbeta3-Integrins etablierten Tracer, verglichen. Untersuchungen ergaben, dass 68Ga-NOTA-NGR einen vielversprechenden neuen PET-Tracer f{\"u}r die Visualisierung und Quantifizierung der APN-Expression im Rahmen der Angiogenese nach einem Myokardinfarkt darstellt. 68Ga-NOTA-NGR zeigte eine erh{\"o}hte Aufnahme im Bereich des Myokardinfarkts im Sinne einer vermehrten Angiogenese. Die Aufnahme des Tracers in infarzierten Arealen war quantitativ h{\"o}her als in der Untersuchung mit 68Ga-NOTA-RGD. In Autoradiographie-Experimenten wurde 68Ga-NOTA-NGR ex vivo untersucht. Die Akkumulation von 68Ga-NOTA-NGR im isch{\"a}mischen Bereich war deutlich h{\"o}her als im gesunden Myokard. Der Nachweis der unterschiedlichen Bereiche des Herzens erfolgte mit HE-F{\"a}rbung. Die Expression von APN wurde immunohistochemisch mittels spezifischer Antik{\"o}rper best{\"a}tigt. Zum Vergleich wurden ebenso einige andere an der Angiogenese beteiligte Faktoren untersucht. APN stellte sich auch hier als geeignetes Target zum Nachweis der Angiogenese heraus. Um die Protease FAP mittels PET zu untersuchen, wurden eine Reihe peptidomimetischer Inhibitoren, die die Erkennungssequenz Glycin-Prolin mit einer Carbonitril-Gruppe als elektrophiler Einheit zur kovalent-reversiblen Hemmung des Enzyms enthalten, entwickelt. Ausgehend vom N-Acetylglycin-pyrrolidin-(2S)-carbonitril als Leitstruktur wurden Inhibitoren und Vorstufen zur Radiomarkierung inkl. verschieden substituierter Benzoes{\"a}uren dargestellt. Zus{\"a}tzlich wurden noch bereits bekannte Inhibitoren synthetisiert, die zum Vergleich in den Enzymassays dienten. Drei Verbindungen zeigten gute inhibitorische Wirkung an FAP und außerdem Selektivit{\"a}t gegen{\"u}ber DPP IV. Keine der entwickelten Verbindungen zeigte einen KI-Wert im nanomolaren Bereich, erforderlich f{\"u}r einen potentiellen Tracer zur in-vivo-Visualisierung einer Enzymexpression mittels PET. Um die Inhibitoren mit der besten Hemmung an FAP zum PET-Tracer weiterzuentwickeln, mussten sie mit einem Positronenemitter markiert werden. Die Markierung erfolgte {\"u}ber Isotopenaustausch, bei dem nicht-radioaktives Iod am aromatischen Ring des Precursors durch das radioaktive Iod-124 (124I) substituiert wurde. Es konnten dadurch die radioiodierten Verbindungen 1-(2-[124I]Iodhippurs{\"a}ure)-pyrrolidin-(2S)-carbonitril und 1-(4-[124I]Iod-hippurs{\"a}ure)-pyrrolidin-(2S)-carbonitril synthetisiert werden. Trotz der relativ niedrigen Affinit{\"a}t f{\"u}r FAP wurde das neue 1-(2-[124I]Iodhippurs{\"a}ure)-pyrrolidin-(2S)-carbonitril in Ratten am Infarktmodell mittels Kleintier-PET getestet. Die Lage der isch{\"a}mischen Zone wurde im Anschluss durch HE-F{\"a}rbung bestimmt. In vivo zeigte sich eine nur sehr geringe Aufnahme des Radiopharmakons in der isch{\"a}mischen Zone des Myokards. Damit ist 1-(2-[124I]Iod-hippurs{\"a}ure)-pyrrolidin-(2S)-carbonitril kein f{\"u}r den gew{\"u}nschten Zweck geeigneter PET-Tracer. Nichtsdestotrotz war der Ansatz vielversprechend und es wurde zum ersten Mal ein PET-Tracer dieser Art zur Untersuchung des FAP im Myokardinfarkt hergestellt.},
  subject      = {Positronen-Emissions-Tomographie},
  language  = {de}
}
@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}
}
@phdthesis{Vershenya2007,
  author    = {Vershenya, Stanislav},
  title     = {T-cell receptor assay and reticulocyte-micronuclei assay as biological dosimeters for ionizing radiation in humans},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28885},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {In radiation accidents biological methods are used in dosimetry, if the radiation dose could not be measured by physical methods. The knowledge of individual dose is a prerequisite for planning a medical treatment and for health risk evaluations. In the present work two biodosimetrical assays were calibrated in young patients who were treated with radioiodine for thyroid cancer. Patients were from Belarus. They suffered from radiation induced thyroid cancer as a consequence of the Chernobyl reactor accident. In radioiodine therapy (RIT) bone marrow and lymphatic organs are exposed to ionizing radiation at doses of 0.1 to 0.75 Sv within about 2 days. Since several RIT have to be applied with interval between each of them from 6 months up to approximately 1 year, total dose can be up to 2 Sv within 2 to 3 years. The dose for thyroid tissue is approximately 1000 times higher. The dose-response relationship was measured by the T-cell receptor test (TCR test) in T4 lymphocytes with and without in vitro incubation or by the micronucleus assay in transferrin receptor positive reticulocytes (MN-Tf-Ret test). In all these assays, the frequency of radiation-induced mutants of blood cells is measured using flow cytometry. The TCR test is a cumulative biodosimeter, which measures the total radiation dose within the last 5 to 10 years, whereas the result of the MN-Tf-Ret test reflects the radiation dose of approximately 24 hours interval. It takes 8 hours and 3 days to perform TCR and MN-Tf-Ret tests respectively. Calibration curves based on radioiodine treated patients can be used for dose estimation in humans, if the radiation conditions correspond to those in RIT. This limits their applicability to low dose-rate \&\#946;- and \&\#947;-irradiation and to doses per session not higher than about 0.5 Sv. If higher doses or dose-rates as well as the other types of ionizing radiation are involved, calibration curves in animals are indispensable. In the case MN-Tf-Ret test mouse models are established and may be used. The TCR assay was performed in 72 thyroid cancer patients aged between 14 and 25. T-cell mutant frequency (Mf) reaches its maximum only after half a year following the RIT. Then it declines exponentially. This decline could be described by the 3 parameter single exponential decay function. Based on this equation, the radiation dose could be calculated when the Mf and the time interval since exposure are known. Furthermore, the experimentally measured Mf value, which significantly exceeds the corresponding calculated Mf value would indicate an individual with higher radiosensitivity. However, among our patients there were none. The reticulocytes micronuclei test (MN-Tf-Ret) was performed in 46 radioiodine treated patients. When measuring the MN frequency (f(MN-Tf-Ret)) the measured cell fraction should be limited only to the youngest cohort of reticulocytes, because all the micronucleated erythrocytes are quickly removed from the peripheral blood by spleen. Thus, the MN test was performed only in CD71 positive (having transferring receptor) reticulocytes. These reticulocytes just entered the peripheral blood flow from red marrow. The MN frequency was measured before the therapy and then every day after the irradiation until day 7. MN frequency curve has typical shape with latent period for days 0 to 3. Then there is a sharp increase in MN frequency which lasts for 24 hours and could start between days 3 and 4. In the following days the MN frequency is dropping to its base level that equals the one before the treatment. The decay of MN frequency is depending on the half-life of radioiodine in the patient organism. If the half-life is low, then the increased f(MN-Tf-Ret) lasts shorter and vice versa. It was shown that the MN frequency curve could be described by the model where all the micronuclei arise only through the last mitosis of erythroblasts in the red marrow and the MN frequency is proportional to the radiation dose in the last cell cycle. The shape of this curve depends on the cell kinetics of erythropoiesis on one side and the exponential decay of radioiodine activity on the other. To the best of our knowledge, the MN-Tf-Ret test was applied in the present study for the first time in biological dosimetry.},
  subject      = {T-Lymphozyten-Rezeptor},
  language  = {en}
}
@article{LapaKircherSchirbeletal.2017,
  author    = {Lapa, Constantin and Kircher, Stefan and Schirbel, Andreas and Rosenwald, Andreas and Kropf, Saskia and Pelzer, Theo and Walles, Thorsten and Buck, Andreas K. and Weber, Wolfgang A. and Wester, Hans-Juergen and Herrmann, Ken and L{\"u}ckerath, Katharina},
  title     = {Targeting CXCR4 with [\(^{68}\)Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?},
  series = {Oncotarget},
  volume    = {8},
  journal   = {Oncotarget},
  number    = {57},
  doi       = {10.18632/oncotarget.18235},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169989},
  pages     = {96732-96737},
  year      = {2017},
  abstract  = {C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [\(^{68}\)Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [\(^{68}\)Ga]Pentixafor-PET/CT. 2′-[\(^{18}\)F]fluoro-2′-deoxy-D-glucose ([\(^{18}\)F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up. Whereas [\(^{18}\)F]FDG-PET depicted active lesions in all patients, [\(^{68}\)Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [\(^{68}\)Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed. In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.},
  language  = {en}
}