One-step ¹⁸F-labeling and preclinical evaluation of prostate specific membrane antigen trifluoroborate probes for cancer imaging.

Abstract

Following the identification of the high-affinity glutamate-ureido scaffold, the design of several potent ¹⁸F- and ⁶⁸Ga-labeled tracers has allowed spectacular progress in imaging recurrent prostate cancer by targeting the prostate specific membrane antigen (PSMA). We evaluated a series of PSMA-targeting probes that are ¹⁸F-labeled in a single step for PET imaging of prostate cancer. Methods: We prepared eight trifluoroborate constructs for prostate cancer imaging, to study the influence of the linker and the trifluoroborate prosthetic on pharmacokinetics and image quality. After one-step labeling by ¹⁹F-¹⁸F isotopic exchange, the radiotracers were injected in mice bearing LNCaP xenografts, with or without blocking controls, to assess specific uptake. PET/CT images and biodistribution data were acquired at 1 h post-injection and compared with [¹⁸F]DCFPyL on the same mouse strain and tumor model. Results: All tracers exhibited nanomolar affinities, were labeled in good radiochemical yields at high molar activities, and exhibited high tumor uptake in LNCaP xenografts with clearance from non-target organs. Most derivatives with a naphthylalanine linker showed significant gastrointestinal excretion. A radiotracer incorporating this linker with a dual trifluoroborate-glutamate labeling moiety showed high tumor uptake, low background activity and no liver or gastrointestinal track accumulation. Conclusion: PSMA-targeting probes with trifluoroborate prosthetic groups represent promising candidates for prostate cancer imaging, due to facile labeling while affording high tumor uptake values and contrast ratios that are similar to those obtained with [¹⁸F]DCFPyL.