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000863491 1001_ $$0P:(DE-Juel1)176188$$aZlatopolskiy, Boris$$b0$$eCorresponding author$$ufzj
000863491 245__ $$aDiscovery of 18F-JK-PSMA-7, a PET Probe for the Detection of Small PSMA-Positive Lesions
000863491 260__ $$aNew York, NY$$bSoc.$$c2019
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000863491 520__ $$aProstate specific membrane antigen (PSMA) expressed by the vast majority of prostate cancers (PCa) is a promising target for PCa imaging. The application of PSMA specific 18F-labeled PET probes like 18F-DCFPyL and 18F-PSMA-1007 considerably improved the accuracy of PCa tumor detection. However, there remains a need for further improvements regarding 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+ LNCaP C4-2 and PSMA– PC-3 cells was compared to that of 18F-DCFPyL. The most promising candidates were additionally evaluated by µPET in healthy rats using PSMA+ peripheral ganglia as a model for small PCa lesions. PET images of the ligand with the best outcome, 18F-JK-PSMA-7, were compared to those of 18F-DCFPyL, 18F-PSMA-1007 and 68GaPSMA-11 with respect to key image quality parameters for the time frame 60-120 min. Results: Compared to 18F-DCFPyL, 18F-JK-PSMA-7 demonstrated increased PSMA specific cellular uptake. While 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 compared to 18F-DCFPyL and 68Ga-PSMA-11. Image resolution was similar for all four 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.
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000863491 7001_ $$0P:(DE-HGF)0$$aEndepols, Heike$$b1
000863491 7001_ $$0P:(DE-Juel1)169356$$aKrapf, Philipp$$b2$$ufzj
000863491 7001_ $$0P:(DE-Juel1)176549$$aGuliyev, Mehrab$$b3$$ufzj
000863491 7001_ $$0P:(DE-Juel1)176705$$aUrusova, Elizaveta A.$$b4$$ufzj
000863491 7001_ $$0P:(DE-Juel1)169321$$aRicharz, Raphael$$b5
000863491 7001_ $$0P:(DE-HGF)0$$aHohberg, Melanie$$b6
000863491 7001_ $$0P:(DE-HGF)0$$aDietlein, Markus$$b7
000863491 7001_ $$0P:(DE-Juel1)177611$$aDrzezga, Alexander$$b8$$ufzj
000863491 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, Bernd$$b9$$ufzj
000863491 773__ $$0PERI:(DE-600)2040222-3$$a10.2967/jnumed.118.218495$$gVol. 60, no. 6, p. 817 - 823$$n6$$p817 - 823$$tJournal of nuclear medicine$$v60$$x2159-662X$$y2019
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