TY - JOUR
A1 - Chen, Xinyu
A1 - Hirano, Mitsuru
A1 - Werner, Rudolf A.
A1 - Decker, Michael
A1 - Higuchi, Takahiro
T1 - Novel \(^{18}\)F-labeled PET Imaging Agent FV45 targeting the Renin-Angiotensin System
JF - ACS Omega
N2 - 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.
KW - FV45
KW - Positronen-Emissions-Tomografie
KW - renin-angiotensin system
KW - angiotensin II type 1 receptor
KW - valsartan
KW - positron emission tomography
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167144
SN - 2470-1343
N1 - This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html), which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
VL - 3
IS - 9
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Chen, Xinyu
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
T1 - Moving into the Next Era of PET Myocardial Perfusion Imaging - Introduction of Novel \(^{18}\)F-labeled Tracers
JF - The International Journal of Cardiovascular Imaging
N2 - The heart failure (HF) epidemic continues to rise with coronary artery disease (CAD) as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 sec), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel 18F-labeled MPI PET radiotracers (half-life, 110 min), the intrinsic advantages of PET can be combined with exercise testing. Additional advantages of those radiotracers include, but are not limited to: potentially improved cost-effectiveness due to the use of pre-existing delivery systems and superior imaging qualities, mainly due to the shortest positron range among available PET MPI probes. In the present review, widely used PET MPI radiotracers will be reviewed and potential novel 18F-labeled perfusion radiotracers will be discussed.
KW - heart failure with mid-range ejection fraction
KW - Positronenemissionstomografie
KW - coronary artery disease
KW - precision medicine
KW - positron emission tomography
KW - PET
KW - SPECT
KW - myocardial perfusion imaging
KW - MPI
KW - 18F-flurpiridaz
KW - 18FFBnTP
KW - HFmrEF
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169134
SN - 1569-5794
ER -
TY - JOUR
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Koshino, Kazuhiro
A1 - Nose, Naoko
A1 - Mühlig, Saskia
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Lapa, Constantin
A1 - Decker, Michael
A1 - Higuchi, Takahiro
T1 - Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity - Introducing High NET Affinity PET Probe \(^{18}\)F-AF78
JF - Theranostics
N2 - 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.
KW - norepinephrine transporter
KW - T-shaped π-π stacking
KW - nonhuman primates
KW - radiotracer kinetics
KW - cardiac innervation imaging
KW - sympathetic nervous system
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300685
VL - 12
IS - 9
SP - 4446
EP - 4458
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Bundschuh, Ralph A.
A1 - Bundschuh, Lena
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
A1 - Weich, Alexander
A1 - Sheikhbahaei, Sara
A1 - Pienta, Kenneth J.
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Lapa, Constantin
A1 - Rowe, Steven P.
T1 - MI-RADS: Molecular Imaging Reporting and Data Systems – A Generalizable Framework for Targeted Radiotracers with Theranostic Implications
JF - Annals of Nuclear Medicine
N2 - Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader’s confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems.
KW - PET
KW - Positronen-Emissions-Tomografie
KW - prostate cancer
KW - neuroendocrine tumor
KW - prostate-specific membrane antigen (PSMA)
KW - somatostatin receptor (SSTR)
KW - positron emission tomography
KW - theranostics
KW - standardization
KW - RADS
KW - reporting and data systems
KW - personalized medicine
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166995
SN - 0914-7187
ER -
TY - INPR
A1 - Nose, Naoko
A1 - Werner, Rudolf A.
A1 - Ueda, Yuichiro
A1 - Günther, Katharina
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
A1 - Fukushima, Kazuhito
A1 - Edenhofer, Frank
A1 - Higuchi, Takahiro
T1 - Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay
T2 - International Journal of Cardiology
N2 - Background: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. Material and Methods: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F-2-fluoro-2-deoxy-D-glucose (\(^{18}\)F-FDG) and \(^{125}\)I-β-methyl-iodophenyl-pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively. Results: After cardiac differentiation of hiPSC, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. Conclusions: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.
KW - tracer
KW - Stammzelle
KW - induced pluripotent stem cells
KW - cardiomyocytes
KW - fatty acid
KW - stem cell therapy
KW - hiPSC-CM
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-163320
SN - 0167-5273
ER -
TY - JOUR
A1 - Nose, Naoko
A1 - Werner, Rudolf A.
A1 - Ueda, Yuichiro
A1 - Günther, Katharina
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
A1 - Fukushima, Kazuhito
A1 - Edenhofer, Frank
A1 - Higuchi, Takahiro
T1 - Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay
JF - International Journal of Cardiology
N2 - BACKGROUND:
Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay.
MATERIAL AND METHODS:
Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F‑2‑fluoro‑2‑deoxy‑d‑glucose (\(^{18}\)F-FDG) and \(^{125}\)I‑β‑methyl‑iodophenyl‑pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively.
RESULTS:
After cardiac differentiation of hiPSCs, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM.
CONCLUSIONS:
During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications.
KW - tracer
KW - Stammzelle
KW - induced pluripotent stem cells
KW - cardiomyocytes
KW - fatty acid
KW - stem cell therapy
KW - hiPSC-CM
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170699
VL - 269
ER -
TY - JOUR
A1 - Hartrampf, Philipp E.
A1 - Weinzierl, Franz-Xaver
A1 - Buck, Andreas K.
A1 - Rowe, Steven P.
A1 - Higuchi, Takahiro
A1 - Seitz, Anna Katharina
A1 - Kübler, Hubert
A1 - Schirbel, Andreas
A1 - Essler, Markus
A1 - Bundschuh, Ralph A.
A1 - Werner, Rudolf A.
T1 - Matched-pair analysis of [\(^{177}\)Lu]Lu-PSMA I&T and [\(^{177}\)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - Background
Labelled with lutetium-177, the urea-based small molecules PSMA I&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT.
Materials and methods
A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [\(^{177}\)Lu]Lu-PSMA I&T, and a matched cohort of 55 patients treated with [\(^{177}\)Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared.
Results
Toxicity assessment revealed grade III anaemia in a single patient (1.8%) for [\(^{177}\)Lu]Lu-PSMA I&T and five (9.1%) for [\(^{177}\)Lu]Lu-PSMA-617. In addition, one (1.9%) grade III thrombopenia for [\(^{177}\)Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [\(^{177}\)Lu]Lu-PSMA I&T did not differ significantly when compared to patients treated with [\(^{177}\)Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89).
Conclusion
In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.
KW - PSMA I&T
KW - PSMA-617
KW - prostate-specific membrane antigen
KW - prostate cancer
KW - radioligand therapy
KW - matched pair
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324581
VL - 49
IS - 9
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Wakabayashi, Hiroshi
A1 - Bauer, Jochen
A1 - Schütz, Claudia
A1 - Zechmeister, Christina
A1 - Hayakawa, Nobuyuki
A1 - Javadi, Mehrbod S.
A1 - Lapa, Constantin
A1 - Jahns, Roland
A1 - Ergün, Süleyman
A1 - Jahns, Valerie
A1 - Higuchi, Takahiro
T1 - Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis
JF - European Heart Journal Cardiovascular Imaging
N2 - Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis.
Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund’s adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo \(^{18}\)F-FDG PET signalling (R\(^2\) = 0.92) as well as with ex vivo 18F-FDG autoradiography (R\(^2\) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at \(^{18}\)F-FDG decrease).
Conclusion: \(^{18}\)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.
KW - positron emission tomography
KW - Myokarditis
KW - myocarditis
KW - inflammation
KW - 18F-FDG
KW - PET
KW - personalized treatment
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165601
SN - 2047-2404
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Eissler, Christoph
A1 - Hayakawa, Nobuyuki
A1 - Arias-Loza, Paula
A1 - Wakabayashi, Hiroshi
A1 - Javadi, Mehrbod S.
A1 - Chen, Xinyu
A1 - Shinaji, Tetsuya
A1 - Lapa, Constantin
A1 - Pelzer, Theo
A1 - Higuchi, Takahiro
T1 - Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET
JF - Scientific Reports
N2 - In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.
KW - diabetic cardiomyopathy
KW - personalized treatment
KW - precision medicine
KW - ZDF rats
KW - ECG
KW - PET
KW - \(^{18}\)F-fluorodeoxyglucose
KW - \(^{18}\)F-FDG
KW - diabetes
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171765
VL - 8
IS - 17631
ER -
TY - CHAP
A1 - Werner, Rudolf
A1 - Chen, Xinyu
A1 - Lapa, Constantin
A1 - Robinson, Simon
A1 - Higuchi, Takahiro
T1 - Intracellular behavior of the novel sympathetic nerve agent \(^{18}\)F-LMI1195
T2 - Journal of Nuclear Cardiology
N2 - No abstract available.
KW - Herz
KW - PET
KW - sympathetic nerve
KW - autonomic nervous system
KW - 18F-LMI1195
KW - positron emission tomography
KW - heart
KW - cardiac
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161137
SN - 1071-3581
N1 - This is a post-peer-review, pre-copyedit version of an article published in J Nucl Cardiol. ISSN: 1071-3581. Supplement (2017) Aug;24;4: 1461-1496. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12350-017-0984-y
VL - 24
IS - 4 Supplement (2017) Aug
ER -
TY - INPR
A1 - Werner, Rudolf A.
A1 - Bundschuh, Ralph A.
A1 - Bundschuh, Lena
A1 - Javadi, Mehrbod S.
A1 - Leal, Jeffrey P.
A1 - Higuchi, Takahiro
A1 - Pienta, Kenneth J.
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Lapa, Constantin
A1 - Rowe, Steven P.
T1 - Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging
T2 - Journal of Nuclear Medicine
N2 - Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center.
Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed.
Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4%) instances, three readers in 40/125 (32%) and two observers in 27/125 (21.6%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005).
Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.
KW - 18F-DCFPyL
KW - Positronen-Emissions-Tomografie
KW - PSMA-RADS
KW - interreader
KW - interobserver
KW - PSMA
KW - prostate cancer
KW - RADS
KW - reporting and data system
KW - PET
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167788
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Ralph A. Bundschuh, Lena Bundschuh, Mehrbod S. Javadi, Jeffrey P. Leal, Takahiro Higuchi, Kenneth J. Pienta, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Constantin Lapa and Steven P. Rowe. Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on 18F-DCFPyL PET/CT Imaging. J Nucl Med 2018;59:1857-1864 © SNMMI.
ER -
TY - JOUR
A1 - Matsusaka, Yohji
A1 - Chen, Xinyu
A1 - Arias-Loza, Paula
A1 - Werner, Rudolf A.
A1 - Nose, Naoko
A1 - Sasaki, Takanori
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Lapa, Constantin
A1 - Higuchi, Takahiro
T1 - In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [\(^{18}\)F]Me4FDG PET in Rats
JF - Molecular Imaging
N2 - Background. Mediating glucose absorption in the small intestine and renal clearance, sodium glucose cotransporters (SGLTs) have emerged as an attractive therapeutic target in diabetic patients. A substantial fraction of patients, however, only achieve inadequate glycemic control. Thus, we aimed to assess the potential of the SGLT-targeting PET radiotracer alpha-methyl-4-deoxy-4-[\(^{18}\)F]fluoro-D-glucopyranoside ([\(^{18}\)F]Me4FDG) as a noninvasive intestinal and renal biomarker of SGLT-mediated glucose transport. Methods. We investigated healthy rats using a dedicated small animal PET system. Dynamic imaging was conducted after administration of the reference radiotracer 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose ([\(^{18}\)F]FDG), or the SGLT-targeting agent, [\(^{18}\)F]Me4FDG either directly into the digestive tract (for assessing intestinal absorption) or via the tail vein (for evaluating kidney excretion). To confirm the specificity of [18F]Me4FDG and responsiveness to treatment, a subset of animals was also pretreated with the SGLT inhibitor phlorizin. In this regard, an intraintestinal route of administration was used to assess tracer absorption in the digestive tract, while for renal assessment, phlorizin was injected intravenously (IV). Results. Serving as reference, intestinal administration of [\(^{18}\)F]FDG led to slow absorption with retention of % of administered radioactivity at 15 min. [\(^{18}\)F]Me4FDG, however, was rapidly absorbed into the blood and cleared from the intestine within 15 min, leading to markedly lower tracer retention of % (). Intraintestinal phlorizin led to marked increase of [\(^{18}\)F]Me4FDG uptake (15 min, %; vs. untreated controls), supporting the notion that this PET agent can measure adequate SGLT inhibition in the digestive tract. In the kidneys, radiotracer was also sensitive to SGLT inhibition. After IV injection, [\(^{18}\)F]Me4FDG reabsorption in the renal cortex was significantly suppressed by phlorizin when compared to untreated animals (%ID/g at 60 min, vs. untreated controls, ; ). Conclusion. As a noninvasive read-out of the concurrent SGLT expression in both the digestive tract and the renal cortex, [\(^{18}\)F]Me4FDG PET may serve as a surrogate marker for treatment response to SGLT inhibition. As such, [\(^{18}\)F]Me4FDG may enable improvement in glycemic control in diabetes by PET-based monitoring strategies.
KW - Sodium-Glucose Cotransporters (SGLTs)
KW - diabetes
KW - rats
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300708
VL - 2022
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Hänscheid, Heribert
A1 - Leal, Jeffrey P.
A1 - Javadi, Mehrbod S.
A1 - Higuchi, Takahiro
A1 - Lodge, Martin A.
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Lapa, Constantin
A1 - Rowe, Steven P.
T1 - Impact of Tumor Burden on Quantitative [\(^{68}\)Ga]DOTATOC Biodistribution
JF - Molecular Imaging and Biology
N2 - Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([\(^{68}\)Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [\(^{68}\)Ga]DOTATATE, we aimed to quantitatively investigate the biodistribution of [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden.
Procedures: Of the 44 included patients, 36/44 (82%) patients demonstrated suspicious radiotracer uptake on [\(^{68}\)Ga]DOTATOC positron emission tomography (PET)/x-ray computed tomography (CT). Volumes of Interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV\(_{mean}\)) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV\(_{mean}\), maximum standardized uptake value (SUV\(_{max}\)), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman’s rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden.
Results: The median SUV\(_{mean}\) was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV\(_{mean}\) 6.9, SUV\(_{max}\) 35.5, TBM 42.6g, and TBU 1.2%. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV\(_{mean}\) increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV\(_{mean}\) nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3%) vs. higher TBU (>7%), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET.
Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [\(^{68}\)Ga]DOTATOC PET/CT. Potential implications include increased normal organ dose with [\(^{177}\)Lu-DOTA]\(^0\)-D-Phe\(^1\)-Tyr\(^3\)-Octreotide and decreased absolute lesion detection with [\(^{68}\)Ga]DOTATOC in high NET burden.
KW - somatostatin receptor
KW - Positronen-Emissions-Tomografie
KW - quantification
KW - [68Ga]DOTATOC
KW - neuroendocrine tumor
KW - SSTR-PET
KW - theranostics
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170280
ER -
TY - JOUR
A1 - Serfling, Sebastian E.
A1 - Lapa, Constantin
A1 - Dreher, Niklas
A1 - Hartrampf, Philipp E.
A1 - Rowe, Steven P.
A1 - Higuchi, Takahiro
A1 - Schirbel, Andreas
A1 - Weich, Alexander
A1 - Hahner, Stefanie
A1 - Fassnacht, Martin
A1 - Buck, Andreas K.
A1 - Werner, Rudolf A.
T1 - Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT
JF - Molecular Imaging and Biology
N2 - Background
CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs.
Methods
Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden.
Results
Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found.
Conclusions
In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.
KW - CXCR4
KW - C-X-C motif chemokine receptor 4
KW - PET
KW - [68Ga]PentixaFor
KW - [177Lu]/[90Y]PentixaTher
KW - theranostics
KW - endoradiotherapy
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324622
VL - 24
IS - 4
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Kobayashi, Ryohei
A1 - Javadi, Mehrbod Som
A1 - Köck, Zoe
A1 - Wakabayashi, Hiroshi
A1 - Unterecker, Stefan
A1 - Nakajima, Kenichi
A1 - Lapa, Constantin
A1 - Menke, Andreas
A1 - Higuchi, Takahiro
T1 - Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits
JF - Journal of Nuclear Medicine
N2 - Background: \(^{123}\)I-metaiodobenzylguanidine (mIBG) provides independent prognostic value for risk stratification among heart failure patients, but the use of concomitant medication should not impact its quantitative information. We aimed to evaluate the four most-prescribed antidepressants currently used as a first‑line treatment for patients with major depressive disorder (MDD) and their potential on altering mIBG imaging results.
Methods: The inhibition effect of four different types of antidepressants (desipramine, escitalopram, venlafaxine and bupropion) for MDD treatment on \(^{131}\)I-mIBG uptake was assessed by in-vitro cell uptake assays using human neuroblastoma SK-N-SH cells. The half maximal inhibitory concentration (IC50) of tracer uptake was determined from dose-response curves. To evaluate the effects of IV pretreatment with desipramine (1.5 mg/kg) and escitalopram (2.5, 15 mg/kg) on mIBG cardiac uptake, in-vivo planar 123I-mIBG scans in healthy New Zealand White Rabbits were conducted. Results: The IC50 values of desipramine, escitalopram, venlafaxine and bupropion on \(^{131}\)I-mIBG cellular uptake were 11.9 nM, 7.5 μM, 4.92 μM, and 12.9 μM, respectively. At the maximum serum concentration (Cmax, as derived by previous clinical trials), the inhibition rates of 131I-mIBG uptake were 90.6 % for desipramine, 25.5 % for venlafaxine, 11.7 % for bupropion and 0.72 % for escitalopram. A low inhibition rate for escitalopram in the cell uptake study triggered investigation of an in-vivo rabbit model: with dosage considerably higher than clinical practice, the non-inhibitory effect of escitalopram was confirmed. Furthermore, pretreatment with desipramine led to a marked reduction of cardiac 123I-mIBG uptake.
Conclusions: In the present in-vitro binding assay and in-vivo rabbit study, the selective-serotonin reuptake inhibitor escitalopram had no major impact on neuronal cardiac mIBG uptake within therapeutic dose ranges, while other types of first-line antidepressants for MDD treatment led to a significant decrease. These preliminary results warrant further confirmatory clinical trials regarding the reliability of cardiac mIBG imaging, in particular, if the patient’s neuropsychiatric status would not tolerate withdrawal of a potentially norepinephrine interfering antidepressant.
KW - MDD
KW - Antidepressants
KW - depression
KW - 123I-mIBG
KW - antidepressant
KW - cardiac sympathetic nerve system
KW - major depressive disorder
KW - myocardial sympathetic innervation imaging
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161280
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Ryohei Kobayashi, Mehrbod Som Javadi, Zoe Köck, Hiroshi Wakabayashi, Stefan Unterecker, Kenichi Nakajima, Constantin Lapa, Andreas Menke, Takahiro Higuchi. Impact of Novel Antidepressants on Cardiac Metaiodobenzylguanidine (mIBG) Uptake: Experimental Studies in SK-N-SH Cells and Healthy Rabbits. J. Nucl. Med. July 1, 2018, vol. 59, no. 7, 1099-1103. © SNMMI.
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Weich, Alexander
A1 - Higuchi, Takahiro
A1 - Schmid, Jan S.
A1 - Schirbel, Andreas
A1 - Lassmann, Michael
A1 - Wild, Vanessa
A1 - Rudelius, Martina
A1 - Kudlich, Theodor
A1 - Herrmann, Ken
A1 - Scheurlen, Michael
A1 - Buck, Andreas K.
A1 - Kropf, Saskia
A1 - Wester, Hans-Jürgen
A1 - Lapa, Constantin
T1 - Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach
JF - Theranostics
N2 - C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
KW - SSTR
KW - peptide receptor radionuclide therapy
KW - neuroendocrine tumor
KW - [\(^{68}\)Ga]Pentixafor
KW - CXCR4
KW - chemokine receptor
KW - PET/CT
KW - DOTATOC
KW - PRRT
KW - Positronen-Emissions-Tomografie
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158008
VL - 7
IS - 6
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Habacha, Bilêl
A1 - Lütje, Susanne
A1 - Bundschuh, Lena
A1 - Higuchi, Takahiro
A1 - Hartrampf, Philipp
A1 - Serfling, Sebastian E.
A1 - Derlin, Thorsten
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Essler, Markus
A1 - Pienta, Kenneth J.
A1 - Eisenberger, Mario A.
A1 - Markowski, Mark C.
A1 - Shinehouse, Laura
A1 - AbdAllah, Rehab
A1 - Salavati, Ali
A1 - Lodge, Martin A.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Bundschuh, Ralph A.
A1 - Rowe, Steven P.
T1 - High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with \(^{18}\)F-DCFPyL
JF - Molecular Imaging
N2 - No abstract available.
KW - SUV
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300748
VL - 2022
ER -
TY - JOUR
A1 - Hartrampf, Philipp E.
A1 - Weinzierl, Franz-Xaver
A1 - Serfling, Sebastian E.
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Higuchi, Takahiro
A1 - Seitz, Anna Katharina
A1 - Kübler, Hubert
A1 - Buck, Andreas K.
A1 - Werner, Rudolf A.
T1 - Hematotoxicity and nephrotoxicity in prostate cancer patients undergoing radioligand therapy with [\(^{177}\)Lu]Lu-PSMA I&T
JF - Cancers
N2 - (1) Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) has shown remarkable results in patients with advanced prostate cancer. We aimed to evaluate the toxicity profile of the PSMA ligand [\(^{177}\)Lu]Lu-PSMA I&T. (2) Methods: 49 patients with metastatic, castration-resistant prostate cancer treated with at least three cycles of [\(^{177}\)Lu]Lu-PSMA I&T were evaluated. Prior to and after RLT, we compared leukocytes, hemoglobin, platelet counts, and renal functional parameters (creatinine, eGFR, n = 49; [\(^{99m}\)Tc]-MAG3-derived tubular extraction rate (TER), n = 42). Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and KDIGO Society. To identify predictive factors, we used Spearman's rank correlation coefficient. (3) Results: A substantial fraction of the patients already showed impaired renal function and reduced leukocyte counts at baseline. Under RLT, 11/49 (22%) patients presented with nephrotoxicity CTCAE I or II according to creatinine, but 33/49 (67%) according to eGFR. Only 5/42 (13%) showed reduced TER, defined as <70% of the age-adjusted mean normal values. Of all renal functional parameters, absolute changes of only 2% were recorded. CTCAE-based re-categorization was infrequent, with creatinine worsening from I to II in 2/49 (4.1%; GFR, 1/49 (2%)). Similar results were recorded for KDIGO (G2 to G3a, 1/49 (2%); G3a to G3b, 2/49 (4.1%)). After three cycles, follow-up eGFR correlated negatively with age (r = −0.40, p = 0.005) and the eGFR change with Gleason score (r = −0.35, p < 0.05) at baseline. Leukocytopenia CTCAE II occurred only in 1/49 (2%) (CTCAE I, 20/49 (41%)) and CTCAE I thrombocytopenia in 7/49 (14%), with an absolute decrease of 15.2% and 16.6% for leukocyte and platelet counts. Anemia CTCAE II occurred in 10/49 (20%) (CTCAE I, 36/49 (73%)) with a decrease in hemoglobin of 4.7%. (4) Conclusions: After PSMA-targeted therapy using [\(^{177}\)Lu]Lu-PSMA I&T, no severe (CTCAE III/IV) toxicities occurred, thereby demonstrating that serious adverse renal or hematological events are unlikely to be a frequent phenomenon with this agent.
KW - PSMA
KW - radioligand therapy
KW - RLT
KW - \(^{177}\)Lu
KW - nephrotoxicity
KW - hematotoxicity
KW - CTCAE
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254825
SN - 2072-6694
VL - 14
IS - 3
ER -
TY - JOUR
A1 - Kazuhino, Koshino
A1 - Werner, Rudolf A.
A1 - Toriumi, Fuijo
A1 - Javadi, Mehrbod S.
A1 - Pomper, Martin G.
A1 - Solnes, Lilja B.
A1 - Verde, Franco
A1 - Higuchi, Takahiro
A1 - Rowe, Steven P.
T1 - Generative Adversarial Networks for the Creation of Realistic Artificial Brain Magnetic Resonance Images
JF - Tomography
N2 - Even as medical data sets become more publicly accessible, most are restricted to specific medical conditions. Thus, data collection for machine learning approaches remains challenging, and synthetic data augmentation, such as generative adversarial networks (GAN), may overcome this hurdle. In the present quality control study, deep convolutional GAN (DCGAN)-based human brain magnetic resonance (MR) images were validated by blinded radiologists. In total, 96 T1-weighted brain images from 30 healthy individuals and 33 patients with cerebrovascular accident were included. A training data set was generated from the T1-weighted images and DCGAN was applied to generate additional artificial brain images. The likelihood that images were DCGAN-created versus acquired was evaluated by 5 radiologists (2 neuroradiologists [NRs], vs 3 non-neuroradiologists [NNRs]) in a binary fashion to identify real vs created images. Images were selected randomly from the data set (variation of created images, 40%-60%). None of the investigated images was rated as unknown. Of the created images, the NRs rated 45% and 71% as real magnetic resonance imaging images (NNRs, 24%, 40%, and 44%). In contradistinction, 44% and 70% of the real images were rated as generated images by NRs (NNRs, 10%, 17%, and 27%). The accuracy for the NRs was 0.55 and 0.30 (NNRs, 0.83, 0.72, and 0.64). DCGAN-created brain MR images are similar enough to acquired MR images so as to be indistinguishable in some cases. Such an artificial intelligence algorithm may contribute to synthetic data augmentation for "data-hungry" technologies, such as supervised machine learning approaches, in various clinical applications.
KW - AI
KW - Magnetresonanztomografie
KW - artificial intelligence
KW - magnetic resonance imaging
KW - MRI
KW - DCGAN
KW - GAN
KW - stroke
KW - machine learning
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172185
VL - 4
IS - 4
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Higuchi, Takahiro
A1 - Nose, Naoko
A1 - Toriumi, Fujio
A1 - Matsusaka, Yohji
A1 - Kuji, Ichiei
A1 - Kazuhiro, Koshino
T1 - Generative adversarial network-created brain SPECTs of cerebral ischemia are indistinguishable to scans from real patients
JF - Scientific reports
N2 - Deep convolutional generative adversarial networks (GAN) allow for creating images from existing databases. We applied a modified light-weight GAN (FastGAN) algorithm to cerebral blood flow SPECTs and aimed to evaluate whether this technology can generate created images close to real patients. Investigating three anatomical levels (cerebellum, CER; basal ganglia, BG; cortex, COR), 551 normal (248 CER, 174 BG, 129 COR) and 387 pathological brain SPECTs using N-isopropyl p-I-123-iodoamphetamine (123I-IMP) were included. For the latter scans, cerebral ischemic disease comprised 291 uni- (66 CER, 116 BG, 109 COR) and 96 bilateral defect patterns (44 BG, 52 COR). Our model was trained using a three-compartment anatomical input (dataset ‘A’; including CER, BG, and COR), while for dataset ‘B’, only one anatomical region (COR) was included. Quantitative analyses provided mean counts (MC) and left/right (LR) hemisphere ratios, which were then compared to quantification from real images. For MC, ‘B’ was significantly different for normal and bilateral defect patterns (P < 0.0001, respectively), but not for unilateral ischemia (P = 0.77). Comparable results were recorded for LR, as normal and ischemia scans were significantly different relative to images acquired from real patients (P ≤ 0.01, respectively). Images provided by ‘A’, however, revealed comparable quantitative results when compared to real images, including normal (P = 0.8) and pathological scans (unilateral, P = 0.99; bilateral, P = 0.68) for MC. For LR, only uni- (P = 0.03), but not normal or bilateral defect scans (P ≥ 0.08) reached significance relative to images of real patients. With a minimum of only three anatomical compartments serving as stimuli, created cerebral SPECTs are indistinguishable to images from real patients. The applied FastGAN algorithm may allow to provide sufficient scan numbers in various clinical scenarios, e.g., for “data-hungry” deep learning technologies or in the context of orphan diseases.
KW - computational biology and bioinformatics
KW - machine learning
KW - neurology
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300757
VL - 12
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Wakabyashi, Hiroshi
A1 - Chen, Xinyu
A1 - Hirano, Mitsuru
A1 - Shinaji, Tetsuya
A1 - Lapa, Constantin
A1 - Rowe, Steven
A1 - Javadi, Mehrbod
A1 - Higuchi, Takahiro
T1 - Functional renal imaging with \(^{18}\)F-FDS PET in rat models of renal disorders
JF - Journal of Nuclear Medicine
N2 - Background: Precise regional quantitative assessment of renal function is limited with conventional \(^{99m}\)Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-(\(^{18}\)F-fluorosorbitol (\(^{18}\)F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, (\(^{18}\)F-FDS is available via simple reduction from routinely used 2-deoxy-2-(\(^{18}\)F-fluoro-D-glucose ((\(^{18}\)F-FDG). We aimed to further investigate the potential of (\(^{18}\)F-FDS PET as a functional renal imaging agent using rat models of kidney diseases.
Methods: Two different rat models of renal impairment were investigated: Glycerol induced acute renal failure (ARF) by intramuscular administration of glycerol in hind legs and unilateral ureteral obstruction (UUO) by ligation of the left ureter. 24h after these treatments, dynamic 30 min 18F-FDS PET data were acquired using a dedicated small animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with co-injected \(^{99m}\)Tc-diethylenetriaminepentaacetic acid (\(^{99m}\)Tc-DTPA) urine activity. Results: Dynamic PET imaging demonstrated rapid (\(^{18}\)F-FDS accumulation in the renal cortex and rapid radiotracer excretion via kidneys in control healthy rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in ARF rats and UUO-treated kidneys. Measured urine radiotracer concentrations of (\(^{18}\)F-FDS and \(^{99m}\)Tc-DTPA were well correlated (R=0.84, P<0.05).
Conclusions: (\(^{18}\)F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. Advantages of high spatiotemporal resolution of PET imaging and simple tracer production could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.
KW - unilateral ureteral obstruction
KW - Nierenfunktionsstörung
KW - Positronen-Emissions-Tomografie
KW - 18F-FDS
KW - 99mTc-DTPA
KW - PET
KW - renal failure
KW - Glomerular filtration
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161279
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Hiroshi Wakabayashi, Xinyu Chen, Mitsuru Hirano, Tetsuya Shinaji, Constantin Lapa, Steven P. Rowe, Mehrbod S. Javadi and Takahiro Higuchi. Functional renal imaging with 18F-FDS PET in rat models of renal disorders. J Nucl Med. May 1, 2018;vol. 59 no. 5: 828-832. © SNMMI.
ER -
TY - INPR
A1 - Yin, Yafu
A1 - Werner, Rudolf A.
A1 - Higuchi, Takahiro
A1 - Lapa, Constantin
A1 - Pienta, Kenneth J.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Rowe, Steven P.
T1 - Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMARADS- 3B Categories
T2 - Journal of Nuclear Medicine
N2 - Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa.
Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy.
Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0%) PSMA-RADS-3A lesions and 3/14 (21.4%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up.
Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy.
KW - PSMA-RADS-3B
KW - Positronen-Emissions-Tomografie
KW - prostate-specific membrane antigen
KW - prostate cancer
KW - PSMA-targeted PET
KW - PSMA-RADS-3A
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167594
SN - 0161-5505
N1 - This research was originally published in JNM. Yafu Yin, Rudolf A. Werner, Takahiro Higuchi, Constantin Lapa, Kenneth J. Pienta, Martin G. Pomper, Michael A. Gorin, Steven P. Rowe.
Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMA-RADS-3B Categories. J Nucl Med. 2019;60:511-516 © SNMMI.
ER -
TY - CHAP
A1 - Werner, Rudolf
A1 - Kobayashi, Ryohei
A1 - Wakabayashi, Hiroshi
A1 - Lapa, Constantin
A1 - Menke, Andreas
A1 - Higuchi, Takahiro
T1 - Effect of Antidepressants on Radiolabeled Metaiodobenzylguanidine (MIBG) Uptake
T2 - European Heart Journal - Cardiovascular Imaging
N2 - No abstract available.
KW - MIBG
KW - Metaiodobenzylguanidine
KW - mIBG
KW - antidepressants
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161116
SN - 2047-2404
N1 - This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal Cardiovascular Imaging following peer review. The version of
record Eur Heart J Cardiovasc Imaging. ISSN: 2047-2404. Supplement, vol. 18, i52-53, May 2017 is available online at: 10.1093/ehjci/jex080.
VL - 18
IS - Supplement
PB - Oxford University Press
ER -
TY - CHAP
A1 - Werner, Rudolf A.
A1 - Marcus, Charles
A1 - Sheikhbahaei, Sara
A1 - Higuchi, Takahiro
A1 - Solnes, Lilja B.
A1 - Rowe, Steven P.
A1 - Buck, Andreas K.
A1 - Lapa, Constantin
A1 - Javadi, Mehrbod S.
T1 - Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method
T2 - Journal of Nuclear Medicine
N2 - No abstract available.
KW - Parkinson-Krankheit
KW - SPECT
KW - Parkinson
KW - Parkinson Disease
KW - DaTscan
KW - Ioflupane
KW - molecular imaging
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162208
UR - http://jnm.snmjournals.org/content/59/supplement_1/626.abstract
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Charles Marcus, Sara Sheikhbahaei, Takahiro Higuchi, Lilja B. Solnes, Steven P. Rowe, Andreas K. Buck, Constantin Lapa, Mehrbod S. Javadi. Diagnostic Accuracy of Visual Assessment of an Initial DaT-Scan in Comparison to a Fully Automatic Semiquantitative Method. J Nucl Med. May 1, 2018; vol. 59 no. supplement 1:626. © SNMMI.
VL - 59
IS - Supplement No. 1
SP - 626
ER -
TY - JOUR
A1 - Lambertini, Alessandro
A1 - Hartrampf, Philipp E.
A1 - Higuchi, Takahiro
A1 - Serfling, Sebastian E.
A1 - Meybohm, Patrick
A1 - Schirbel, Andreas
A1 - Buck, Andreas K.
A1 - Werner, Rudolf A.
T1 - CXCR4-targeted molecular imaging after severe SARS-Cov-2 infection
JF - European Journal of Nuclear Medicine and Molecular Imaging
N2 - No abstract available.
KW - CXCR4-targeting
KW - SARS-CoV-2
KW - COVID-19
KW - molecular imaging
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324619
VL - 50
IS - 1
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
A1 - Buck, Andreas K.
A1 - Hartrampf, Philipp E.
A1 - Serfling, Sebastian E.
A1 - Scheurlen, Michael
A1 - Wester, Hans-Jürgen
A1 - Meining, Alexander
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Kircher, Malte
T1 - CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
JF - Diagnostics
N2 - We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
KW - CXCR4
KW - NET
KW - NEC
KW - 68Ga-Pentixafor
KW - 18F-FDG
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234231
SN - 2075-4418
VL - 11
IS - 4
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Kircher, Malte
A1 - Schirbel, Andreas
A1 - Wester, Hans-Jürgen
A1 - Buck, Andreas K.
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
T1 - CXCR4-directed imaging in solid tumors
JF - Frontiers in Oncology
N2 - Despite histological evidence in various solid tumor entities, available experience with CXCR4-directed diagnostics and endoradiotherapy mainly focuses on hematologic diseases. With the goal of expanding the application of CXCR4 theranostics to solid tumors, we aimed to elucidate the feasibility of CXCR4-targeted imaging in a variety of such neoplasms.
Methods: Nineteen patients with newly diagnosed, treatment-naïve solid tumors including pancreatic adenocarcinoma or neuroendocrine tumor, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and prostate cancer underwent [\(^{68}\)Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUV\(_{max}\)) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [\(^{68}\)Ga]Pentixafor findings were further compared to immunohistochemistry and [\(^{18}\)F]FDG PET/CT.
Results: On [\(^{68}\)Ga]Pentixafor PET/CT, 10/19 (52.6%) primary tumors were visually detectable with a median SUVmax of 5.4 (range, 1.7–16.0) and a median TBR of 2.6 (range, 0.8–7.4), respectively. The highest level of radiotracer uptake was identified in a patient with cholangiocarcinoma (SUVmax, 16.0; TBR, 7.4). The relatively low uptake on [\(^{68}\)Ga]Pentixafor was also noted in metastases, exhibiting a median SUVmax of 4.5 (range, 2.3–8.8; TBR, 1.7; range, 1.0–4.1). A good correlation between uptake on [\(^{68}\)Ga]Pentixafor and histological derived CXCR4 expression was noted (R = 0.62, P < 0.05). In the 3 patients in whom [\(^{18}\)F]FDG PET/CT was available, [\(^{68}\)Ga]Pentixafor exhibited lower uptake in all lesions.
Conclusions: In this cohort of newly diagnosed, treatment-naïve patients with solid malignancies, CXCR4 expression as detected by [\(^{68}\)Ga]Pentixafor-PET/CT and immunohistochemistry was rather moderate. Thus, CXCR4-directed imaging may not play a major role in the management of solid tumors in the majority of patients.
KW - CXCR4
KW - [68Ga]Pentixafor
KW - theranostics
KW - solid tumors
KW - chemokine receptor
Y1 - 2019
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195678
SN - 2234-943X
VL - 9
IS - 770
ER -
TY - JOUR
A1 - Toyama, Yoshitaka
A1 - Werner, Rudolf A.
A1 - Ruiz-Bedoya, Camilo A.
A1 - Ordonez, Alvaro A.
A1 - Takase, Kei
A1 - Lapa, Constantin
A1 - Jain, Sanjay K.
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Higuchi, Takahiro
T1 - Current and future perspectives on functional molecular imaging in nephro-urology: theranostics on the horizon
JF - Theranostics
N2 - In recent years, a paradigm shift from single-photon-emitting radionuclide radiotracers toward positron-emission tomography (PET) radiotracers has occurred in nuclear oncology. Although PET-based molecular imaging of the kidneys is still in its infancy, such a trend has emerged in the field of functional renal radionuclide imaging. Potentially allowing for precise and thorough evaluation of renal radiotracer urodynamics, PET radionuclide imaging has numerous advantages including precise anatomical co-registration with CT images and dynamic three-dimensional imaging capability. In addition, relative to scintigraphic approaches, PET can allow for significantly reduced scan time enabling high-throughput in a busy PET practice and further reduces radiation exposure, which may have a clinical impact in pediatric populations. In recent years, multiple renal PET radiotracers labeled with C-11, Ga-68, and F-18 have been utilized in clinical studies. Beyond providing a precise non-invasive read-out of renal function, such radiotracers may also be used to assess renal inflammation. This manuscript will provide an overview of renal molecular PET imaging and will highlight the transformation of conventional scintigraphy of the kidneys toward novel, high-resolution PET imaging for assessing renal function. In addition, future applications will be introduced, e.g. by transferring the concept of molecular image-guided diagnostics and therapy (theranostics) to the field of nephrology.
KW - glomerular filtration rate
KW - renal
KW - kidney
KW - renal function
KW - positron emission tomography
KW - nephrology
KW - urology
KW - molecular imaging
KW - theranostics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260090
VL - 11
IS - 12
ER -
TY - CHAP
A1 - Werner, Rudolf
A1 - Hayakawa, Nobuyuki
A1 - Arias-Loza, Paula-Anah
A1 - Wakabayashi, Hiroshi
A1 - Shinaji, Tetsuya
A1 - Lapa, Constantin
A1 - Pelzer, Theo
A1 - Higuchi, Takahiro
T1 - Bildgebung der frühen linksventrikulären Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell
T2 - Nuklearmedizin
N2 - Einleitung: Die linksventrikuläre diastolische Dysfunktion (LVDD) ist bei Diabetikern noch vor Entwicklung einer klinisch apparenten Herzinsuffizienz eines der ersten Anzeichen einer kardialen Beteiligung. Daher soll in dieser Studie untersucht werden, ob die LVDD mit ECG-gated F-18-FDG PET in einem Diabetes-Rattenmodell dargestellt werden kann.
Methodik: Es wurden F-18-FDG PET Scans in einem Typ-2-Diabetes Rattenmodell (ZDF fa/fa, n=6) und in ZL Kontrollen (n=6) vorgenommen (Alter, jeweils 13 Wochen). Unter Hyperinsulinemic-Euglycemic Clamp-Technik wurden 37 MBq 18F-FDG über die Schwanzvene appliziert. 15-35 Minuten nach Tracergabe wurden mittels eines Kleintier-PET-Scanners sowie unter EKG-Ableitung PET Scans angefertigt (16 frames/cardiac cycle). Die linksventrikuläre Ejektionsfraktion (EF) und die Peak Füllrate (PFR) wurden mittels einer geeigneten Software (Heart Function View) gemessen, wobei die Software an die Größe des Rattenherzes angepasst wurde.
Ergebnisse: Im Alter von 13 Wochen entwickeln ZDF Diabetes-Ratten eine im Vergleich zu Kontrolltieren eine signifikante myokardiale Hypertrophie, bestätigt durch post-mortem Analyse des Herzgewichtes (994±78mg vs. 871±44mg in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.01). ECG-gated PET zeigte eine signifikante Abnahme der LV diastolischen PFR (10.4±0.5 vs. 11.8±0.4 EDV/sec in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.001), jedoch zeigte sich kein signifikanter Unterschied zwischen LVEF und der Herzfrequenz in den untersuchten ZDF Diabetes-Ratten und Kontrollen (LVEF: 60.0±4.5 vs. 63.7±4.1%, n.s. und HR: 305±25 vs. 323±24 bpm, n.s.).
Schlussfolgerung: Im Diabetes-Ratten-Modell kann unter Verwendung eines ECG-gated FDG-PET Protokolls die diastolische Dysfunktion als Parameter der frühen diabetischen Kardiomyopathie nachgewiesen werden.
KW - Positronen-Emissions-Tomografie
KW - Diabetes
KW - diabetische Kardiomyopathie
KW - Positronen-Emissions-Tomografie
KW - PET
KW - EKG
KW - ECG
KW - ECG-gated
Y1 - 2017
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161396
UR - http://www.nuklearmedizin.de/jahrestagungen/abstr_online2017/print_abstract_pdf.php
SN - 0029-5566
N1 - This article is not an exact copy of the original published article in Nuklearmedizin.
The definitive publisher-authenticated version of „Bildgebung der frühen linksventrikulären Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell. Nuklearmedizin 2017; 56 (Abstract Nr.: V119).“ is available online at http://www.nuklearmedizin.de/jahrestagungen/abstr_online2017/print_abstract_pdf.php
VL - 56
IS - 2
PB - Schattauer Verlag
ER -
TY - JOUR
A1 - Kosmala, Aleksander
A1 - Serfling, Sebastian E.
A1 - Dreher, Niklas
A1 - Lindner, Thomas
A1 - Schirbel, Andreas
A1 - Lapa, Constantin
A1 - Higuchi, Takahiro
A1 - Buck, Andreas K.
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
T1 - Associations between normal organs and tumor burden in patients imaged with fibroblast activation protein inhibitor-directed positron emission tomography
JF - Cancers
N2 - (1) Background: We aimed to quantitatively investigate [\(^{68}\)Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid cancers underwent a total of 40 [\(^{68}\)Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total tumor burden was determined by manual segmentation of tumor lesions with increased uptake. For tumor burden, quantitative assessment included maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA = TV × SUV\(_{mean}\)). Associations between uptake in normal organs and tumor burden were investigated by applying Spearman's rank correlation coefficient. (3) Results: Median SUV\(_{mean}\) values were 2.15 in the pancreas (range, 1.05–9.91), 1.42 in the right (range, 0.57–3.06) and 1.41 in the left kidney (range, 0.73–2.97), 1.2 in the heart (range, 0.46–2.59), 0.86 in the spleen (range, 0.55–1.58), 0.65 in the liver (range, 0.31–2.11), and 0.57 in the bone marrow (range, 0.26–0.94). We observed a trend towards significance for uptake in the myocardium and tumor-derived SUV\(_{max}\) (ρ = 0.29, p = 0.07) and TV (ρ = −0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUV\(_{max}\) (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high tumor burden, significant correlations of myocardial uptake with tumor SUV\(_{max}\) (ρ = 0.44; p = 0.03) and tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [\(^{68}\)Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher tumor load or uptake may not lead to decreased doses in the majority of normal organs.
KW - PET
KW - [\(^{68}\)Ga]Ga-FAPI
KW - theranostics
KW - radioligand therapy
KW - fibroblast activation protein
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275154
SN - 2072-6694
VL - 14
IS - 11
ER -
TY - INPR
A1 - Werner, Rudolf A.
A1 - Andree, Christian
A1 - Javadi, Mehrbod S.
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Rowe, Steven P.
A1 - Pienta, Kenneth J.
T1 - A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging
T2 - Urology - The Gold Journal
N2 - No abstract available.
KW - 18F-DCFPyL
KW - Virchow Node
KW - PSMA-PET
KW - Virchow Node
KW - Positron Emission Tomography
KW - Prostate Cancer
KW - PET
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161103
SN - 0090-4295
N1 - This is the accepted manuscript of Rudolf Werner, Christian Andree, Mehrbod S. Javadi, Constantin Lapa, Andreas K. Buck, Takahiro Higuchi, Martin G. Pomper, Michael A.Gorin, Steven P.Rowe, Kenneth J. Pienta: A Voice From the Past: Re-Discovering the Virchow Node with PSMA-Targeted 18F-DCFPyL PET Imaging. Published in Urology 117(2018), p. 18-21. https://doi.org/10.1016/j.urology.2018.03.030
N1 - Die finale Version dieses Artikels steht unter https://doi.org/10.1016/j.urology.2018.03.030 oder https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-164632 open access zur Verfügung.
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Andree, Christian
A1 - Javadi, Mehrbod S.
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Rowe, Steven P.
A1 - Pienta, Kenneth J.
T1 - A Voice From the Past: Re-Discovering the Virchow Node with PSMA-targeted \(^{18}\)F-DCFPyL PET Imaging
JF - Urology - The Gold Journal
N2 - No abstract available.
KW - 18F-DCFPyL
KW - PET
KW - PSMA-PET
KW - Positron Emission Tomography
KW - Prostate Cancer
KW - Virchow Node
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164632
SN - 0090-4295
VL - 117
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Derlin, Thorsten
A1 - Lapa, Constantin
A1 - Sheikbahaei, Sara
A1 - Higuchi, Takahiro
A1 - Giesel, Frederik L.
A1 - Behr, Spencer
A1 - Drzezga, Alexander
A1 - Kimura, Hiroyuki
A1 - Buck, Andreas K.
A1 - Bengel, Frank M.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Rowe, Steven P.
T1 - \(^{18}\)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging
JF - Theranostics
N2 - Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
KW - Radiofluorine
KW - prostate-specific membrane antigen
KW - prostate cancer
KW - \(^{18}\)F
KW - PSMA
KW - \(^{68}\)Ga
KW - theranostics
KW - radioligand therapy
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202559
SN - 1838-7640
VL - 10
IS - 1
ER -
TY - JOUR
A1 - Nose, Naoko
A1 - Nogami, Suguru
A1 - Koshino, Kazuhiro
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Kashima, Soki
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Fukuchi, Kazuki
A1 - Higuchi, Takahiro
T1 - [18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species
JF - Scientific Reports
N2 - Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n=1), rats (n=4), rabbits (n=4) and non-human primates (n=3), via carotid artery in rats (n=4) and non-human primates (n=3), and via intra-myocardial injection in rats (n=5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.
KW - biomarkers
KW - molecular medicine
KW - stem-cell research
KW - stem cells
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260590
VL - 11
IS - 1
ER -