Imidazolium-methylene-trifluoroborate: A novel radioprosthetic group validated with preclinical 18F-Positron Emission Tomography imaging of Prostate Specific Membrane Antigen in mice

Abstract

Organotrifluoroborates have gained acceptance as radioprosthetic groups for radiofluorination. Of these, the zwitterionic prosthetic group “AMBF₃” with a quaternary dimethylammonium ion dominates the trifluoroborate space. Herein, we report on imidazolium-methylene trifluoroborate (ImMBF₃) as an alternative radioprosthetic group and report on its properties in the context of a PSMA-targeting EUK ligand that was previously been conjugated to AMBF₃. The ImMBF₃ is readily synthesized from imidazole and conjugated via CuAAC “click” chemistry to give a structure similar to PSMA-617. ¹⁸F-labeling proceeded in one step per our previous reports and imaged in LNCaP-xenograft bearing mice. The [¹⁸F]-PSMA-617-ImMBF₃ tracer proved to be less polar (LogP_7.4 = −2.95 ± 0.03) while showing a significantly lower solvolytic rate (t_1/2 = 8100 min) and slightly higher molar activity (Am) at 174 ± 38 GBq/μmol. Tumor uptake was measured at 13.7 ± 4.8%ID/g and a tumor:muscle ratio of 74.2 ± 35.0, tumor:blood ratio of 21.4 ± 7.0, tumor:kidney ratio of 0.29 ± 0.14, and tumor:bone ratio of 23.5 ± 9.5. In comparison with previously reported PSMA-targeting EUK-AMBF₃ conjugates, we have altered the LogP_7.4 value, tuned the solvolytic half-life of the prosthetic, and increased radiochemical conversion while achieving similar tumor uptake, contrast ratios, and molar activities compared with AMBF₃ bioconjugates.