RT Journal Article SR Electronic T1 Synthesis and Biologic Evaluation of Novel 18F-Labeled Probes Targeting Prostate-Specific Membrane Antigen for PET of Prostate Cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1978 OP 1984 DO 10.2967/jnumed.116.175810 VO 57 IS 12 A1 Naoya Harada A1 Hiroyuki Kimura A1 Satoru Onoe A1 Hiroyuki Watanabe A1 Daiko Matsuoka A1 Kenji Arimitsu A1 Masahiro Ono A1 Hideo Saji YR 2016 UL http://jnm.snmjournals.org/content/57/12/1978.abstract AB Prostate-specific membrane antigen (PSMA) is a membrane protein highly expressed on prostate cancer cells and a potential imaging target for diagnosis. 18F-DCFPyL has been recently developed as an effective probe with high diagnostic accuracy for prostate cancer imaging. However, its radiochemical yield is low. We developed new PSMA probes using succinimidyl 4-18F-fluorobenzoate (18F-SFB), a rapid and effective 18F-labeling agent, taking advantage of the high radiochemical yield of this compound. We evaluated the probes as PET probes for PSMA imaging. Methods: Four 18F-labeled probes, 18F-8a, 18F-8b, 18F-10a, and 18F-10b, were synthesized using 18F-SFB, and their affinity for PSMA and partition coefficients (log D) were evaluated in vitro. Biodistribution studies were performed in human prostate cancer xenograft–bearing mice. PET images were obtained using 2 compounds, 18F-8a and 18F-10a, and a toxicologic study of 18F-10a was performed. Results: Four 18F-labeled asymmetric urea compounds, conjugated with 18F-SFB, were synthesized at a radiochemical yield of 30%–50% (decay-corrected), with a radiochemical purity greater than 95%. The radiochemical yield was 10–15 times higher than that of 18F-DCFPyL, the probe currently used in clinical studies. All 4 compounds showed high affinity for PSMA. 18F-8a and 18F-10a had a particularly high binding affinity (Ki values of 3.35 and 2.23 nM, respectively). In the biodistribution study, the accumulation of 18F-8a (13.3 ± 2.2 percentage injected dose per gram [%ID/g]) and 18F-10a (14.0 ± 3.1 %ID/g) in PSMA-positive human prostate (LNCaP) tumors was higher than that of the other 2 compounds and similar to that of 18F-DCFPyL (16.0 ± 2.9 %ID/g). 18F-10a showed the lowest hepatic and intestinal accumulation among the 4 compounds and slightly slower blood clearance than others. In the PET imaging studies, 18F-8a and 18F-10a were clearly visualized in LNCaP in xenograft-bearing mice. 18F-10a showed higher LNCaP-to-liver ratios than 18F-8a. We confirmed the safety profiles of 18F-10a; the no-observed-adverse-effects level was larger than 13.2 μg/kg. Conclusion: A novel 18F-labeled asymmetric urea compound, 18F-10a, had a high radiochemical yield, high binding affinity for PSMA, and pharmacokinetic profiles suitable for a PSMA imaging probe. We believe that 18F-10a can be effectively and safely used in this type of imaging.