Imidazolium-Methylene-Trifluoroborate: a Novel Radioprosthetic Group Validated with Preclinical 18 F-PET Imaging of PSMA in Mice.

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-methylenetrifluoroborate (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 (LogP7.4 = -2.95 ± 0.03) while showing a significantly lower solvolytic rate (t1/2 = 8,100 mins) 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 comparing to previously reported PSMA-targeting EUK-AMBF3 conjugates, we have altered the LogP7.4 value, tuned the solvolytic half-life of the prosthetic, and increased radiochemical conversion, while achieving similar tumor uptake, contrast ratios, and molar activities compared to AMBF3 bioconjugates.