Grant: Travel Awards - Institute Community Support

The past decade has seen the development of many PET radiotracers targeting the Prostate-Specific Membrane Antigen (PSMA) for prostate cancer (PCa) imaging, including radiometal chelation or 18F-radiofluorination. Given the great interest in imaging PSMA for PCa diagnosis, a rapid, one-step, user-friendly, aqueous fluorination reaction that can be applied to PSMA-ligands would be of great utility. Moreover, excellent images, defined by high tumor uptake values and high T:NT ratios would be equally essential to advance such a tracer to clinical applications. Organotrifluoroborates prosthetics afford very efficient, kit-like, one-step 18F-labeling by isotope exchange (IEX). Here we have used this approach to prepare trifluroroborate derivatives of the Glu-Lys diureido scaffold to combine the advantages of one-step aqeous labeling with the production of a PSMA-specific tracer. This new conjugate was labeled in yields of 10-15%, at specific activities of >104 GBq/umol. PET imaging and correlated ex-vivo biodistribution show substantial clearance to bladder with high tumor uptake (25±8 %ID/g) along with typically high kidney uptake (81±31 %ID/g). Excellent T:Bone (35±27), T:Muscle (145±57) and T:Blood (19±8) ratios were observed. Blocking by co-injection with DCFPyL (0.5 mg) reduced >95% uptake demonstrating specific uptake by PSMA. Here we show several salient points: 1) IEX on organotrifluoroborates afford the simplicity of a one-step labeling without pre-drying of the 18F-fluoride; 2) Radiosynthesis proceeds in a clinical setting within a fully shielded hotcell within 30 min or less in reasonable yields and high specific activities; 3) Purification involves a simple Sep-Pak elution 4) Images show excellent tumor uptake values and exceptionally high T:M and T:B ratios, values that compare favorably to or exceed those seen with 18F-DCFPyL. These data suggest that this compound or a closely related analog will be suitable for human clinical applications.