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Prostate-specific membrane antigen (PSMA), expressed by most prostate carcinomas (PCa), is a promising target for PCa imaging. The application of PSMA-specific 18 F-labeled PET probes such as 18 F-DCFPyL and 18 F-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 18 F-DCFPyL, 18 F-PSMA-1007, and 68 Ga-PSMA-11. Methods: Eight novel 18 F-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 18 F-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, 18 F-JK-PSMA-7, were compared with those of 18 F-DCFPyL, 18 F-PSMA-1007, and 68 Ga-PSMA-11 with respect to key image-quality parameters for the time frame 60-120 min. Results: Compared with 18 F-DCFPyL, 18 F-JK-PSMA-7 demonstrated increased PSMA-specific cellular uptake. Although target-to-background ratios of 18 F-DCFPyL and 18 F-PSMA-1007 were comparable, this parameter was higher for 18 F-JK-PSMA-7 and lower for 68 Ga-PSMA-11. Image acutance was significantly higher for 18 F-JK-PSMA-7 and 18 F-PSMA-1007 than for 18 F-DCFPyL and 68 Ga-PSMA-11. Image resolution was similar for all 4 tracers. 18 F-PSMA-1007 demonstrated significantly higher blood protein binding and bone uptake than the other tracers. Conclusion:  18 F-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.

Discovery of 18F-JK-PSMA-7, a PET Probe for the Detection of Small PSMA-Positive Lesions

Discovery of ¹⁸F-JK-PSMA-7, a PET Probe for the Detection of Small PSMA-Positive Lesions