Boris D Zlatopolskiy1,2,3, Heike Endepols1,2,4, Philipp Krapf1,2, Mehrab Guliyev1, Elizaveta A Urusova1,2, Raphael Richarz1,2, Melanie Hohberg4, Markus Dietlein4, Alexander Drzezga4, Bernd Neumaier5,2,3. 1. Institute of Radiochemistry and Experimental Molecular Imaging, University Hospital of Cologne, Cologne, Germany. 2. Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Jülich GmbH, Jülich, Germany. 3. Max Planck Institute for Metabolism Research, Cologne, Germany; and. 4. Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany. 5. Institute of Radiochemistry and Experimental Molecular Imaging, University Hospital of Cologne, Cologne, Germany b.neumaier@fz-juelich.de.
Abstract
Prostate-specific membrane antigen (PSMA), expressed by most prostate carcinomas (PCa), is a promising target for PCa imaging. The application of PSMA-specific 18F-labeled PET probes such as 18F-DCFPyL and 18F-PSMA-1007 considerably improved the accuracy of PCa tumor detection. However, there remains a need for further improvements in sensitivity and specificity. The aim of this study was the development of highly selective and specific PSMA probes with enhanced imaging properties, in comparison with 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11. Methods: Eight novel 18F-labeled PSMA ligands were prepared. Their cellular uptake in PSMA-positive LNCaP C4-2 and PSMA-negative PC-3 cells was compared with that of 18F-DCFPyL. The most promising candidates were additionally evaluated by small-animal PET in healthy rats using PSMA-positive peripheral ganglia as a model for small PCa lesions. PET images of the ligand with the best outcome, 18F-JK-PSMA-7, were compared with those of 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11 with respect to key image-quality parameters for the time frame 60-120 min. Results: Compared with 18F-DCFPyL, 18F-JK-PSMA-7 demonstrated increased PSMA-specific cellular uptake. Although target-to-background ratios of 18F-DCFPyL and 18F-PSMA-1007 were comparable, this parameter was higher for 18F-JK-PSMA-7 and lower for 68Ga-PSMA-11. Image acutance was significantly higher for 18F-JK-PSMA-7 and 18F-PSMA-1007 than for 18F-DCFPyL and 68Ga-PSMA-11. Image resolution was similar for all 4 tracers. 18F-PSMA-1007 demonstrated significantly higher blood protein binding and bone uptake than the other tracers. Conclusion: 18F-JK-PSMA-7 is a promising candidate for high-quality visualization of small PSMA-positive lesions. Excellent preclinical imaging properties justify further preclinical and clinical studies of this tracer.
Prostate-specific membrane antigen (PSMA), expressed by most prostate carcinomas (PCa), is a promising target for PCa imaging. The application of PSMA-specific 18F-labeled PET probes such as 18F-DCFPyL and 18F-PSMA-1007 considerably improved the accuracy of PCa tumor detection. However, there remains a need for further improvements in sensitivity and specificity. The aim of this study was the development of highly selective and specific PSMA probes with enhanced imaging properties, in comparison with 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11. Methods: Eight novel 18F-labeled PSMA ligands were prepared. Their cellular uptake in PSMA-positive LNCaPC4-2 and PSMA-negative PC-3 cells was compared with that of 18F-DCFPyL. The most promising candidates were additionally evaluated by small-animal PET in healthy rats using PSMA-positive peripheral ganglia as a model for small PCa lesions. PET images of the ligand with the best outcome, 18F-JK-PSMA-7, were compared with those of 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11 with respect to key image-quality parameters for the time frame 60-120 min. Results: Compared with 18F-DCFPyL, 18F-JK-PSMA-7 demonstrated increased PSMA-specific cellular uptake. Although target-to-background ratios of 18F-DCFPyL and 18F-PSMA-1007 were comparable, this parameter was higher for 18F-JK-PSMA-7 and lower for 68Ga-PSMA-11. Image acutance was significantly higher for 18F-JK-PSMA-7 and 18F-PSMA-1007 than for 18F-DCFPyL and 68Ga-PSMA-11. Image resolution was similar for all 4 tracers. 18F-PSMA-1007 demonstrated significantly higher blood protein binding and bone uptake than the other tracers. Conclusion: 18F-JK-PSMA-7 is a promising candidate for high-quality visualization of small PSMA-positive lesions. Excellent preclinical imaging properties justify further preclinical and clinical studies of this tracer.
Authors: Ying Chen; Mrudula Pullambhatla; Catherine A Foss; Youngjoo Byun; Sridhar Nimmagadda; Srinivasan Senthamizhchelvan; George Sgouros; Ronnie C Mease; Martin G Pomper Journal: Clin Cancer Res Date: 2011-10-31 Impact factor: 12.531
Authors: Zsolt Szabo; Esther Mena; Steven P Rowe; Donika Plyku; Rosa Nidal; Mario A Eisenberger; Emmanuel S Antonarakis; Hong Fan; Robert F Dannals; Ying Chen; Ronnie C Mease; Melin Vranesic; Akrita Bhatnagar; George Sgouros; Steve Y Cho; Martin G Pomper Journal: Mol Imaging Biol Date: 2015-08 Impact factor: 3.488
Authors: Ryan P Murelli; Andrew X Zhang; Julien Michel; William L Jorgensen; David A Spiegel Journal: J Am Chem Soc Date: 2009-12-02 Impact factor: 15.419
Authors: Jeffrey S Ross; Christine E Sheehan; Hugh A G Fisher; Ronald P Kaufman; Prabhjot Kaur; Karen Gray; Iain Webb; Gary S Gray; Rebecca Mosher; Bhaskar V S Kallakury Journal: Clin Cancer Res Date: 2003-12-15 Impact factor: 12.531
Authors: Falguni Basuli; Tim E Phelps; Xiang Zhang; Carolyn C Woodroofe; Jyoti Roy; Peter L Choyke; Rolf E Swenson; Elaine M Jagoda Journal: Pharmaceuticals (Basel) Date: 2022-05-13
Authors: Wojciech Cytawa; Anna Katharina Seitz; Stefan Kircher; Kazuhito Fukushima; Johannes Tran-Gia; Andreas Schirbel; Tomasz Bandurski; Piotr Lass; Markus Krebs; Wojciech Połom; Marcin Matuszewski; Hans-Jürgen Wester; Andreas K Buck; Hubert Kübler; Constantin Lapa Journal: Eur J Nucl Med Mol Imaging Date: 2019-09-16 Impact factor: 9.236
Authors: Francesco Ceci; Daniela E Oprea-Lager; Louise Emmett; Judit A Adam; Jamshed Bomanji; Johannes Czernin; Matthias Eiber; Uwe Haberkorn; Michael S Hofman; Thomas A Hope; Rakesh Kumar; Steven P Rowe; Sarah M Schwarzenboeck; Stefano Fanti; Ken Herrmann Journal: Eur J Nucl Med Mol Imaging Date: 2021-02-19 Impact factor: 9.236
Authors: Heike Endepols; Agnieszka Morgenroth; Boris D Zlatopolskiy; Philipp Krapf; Johannes Zischler; Raphael Richarz; Sergio Muñoz Vásquez; Bernd Neumaier; Felix M Mottaghy Journal: BMC Cancer Date: 2019-06-26 Impact factor: 4.430
Authors: Rudolf A Werner; Thorsten Derlin; Constantin Lapa; Sara Sheikbahaei; Takahiro Higuchi; Frederik L Giesel; Spencer Behr; Alexander Drzezga; Hiroyuki Kimura; Andreas K Buck; Frank M Bengel; Martin G Pomper; Michael A Gorin; Steven P Rowe Journal: Theranostics Date: 2020-01-01 Impact factor: 11.556