A new 18F-RBF3 radioprosthetic for one step aqueous labeling of peptides and other ligands: meeting the challenge of radiosynthetic ease and preclinical impact i.e. high specific activity and high T:NT ratios

223Objectives To validate a new RBF3 for one-step 18F-labeling of complex bioactive tracers that includes: 1) no azeotropic drying, 2) use of Curie-levels of NCA 18F-fluoride, 3) rapidity e.g. 15-20 min, 4) no HPLC purification, 5) use of micrograms of precursor, 6) good-to-excellent tumor uptake, 7) very high T:NT ratios, 8) no bone uptake, 9) general applicability to several complex peptides.Methods We designed a novel zwitterionic organotrifluoroborate that is "click" conjugated to various peptides.[1,2] For labeling, we have identified QMA resins that enable direct elution of  1Ci of NCA 18F-fluoride into <60 μL of PBS saline into an Eppendorf tube containing <100 nmol of bioconjugate-RBF3 precursor in buffered DMF. Following heating at 80○ for 15-20 min, the tracer is purified by a simple C18-Sep-Pak push with ethanol-saline elution. Unpublished analogs of bombesin, octreotate, bradykinin, trimeric-RGD, and a trimeric CA-IX inhibitor were labeled and injected into mice with suitable xenograft tumors with blocking controls.Results RCYs are routinely >25% (n>70). Standard curve analysis shows SA's are >3 Ci/μmol. QC radio/UV HPLC traces show purity >98%. Tumor:non-tumor ratios (T:M and T:Bone) are typically >20 and often exceptionally high (>75). T:Blood ratios are >6, and often much higher.Conclusions Bioconjugates with a novel organotrifluoroborate are eaily synthesized and stocked in aliquots of <100 ug for on-demand, one-step aqueous 18F-labeling using 1 Ci of NCA 18F-fluoride in fully shielded hot-cells. Labeling occurs in 15 min with good yields (e.g. 200-300 mCi) at high SA (>3 Ci/μmol) and excellent purity. HPLC purification is obviated. The synthetic ease for coupling this new RBF3 to peptides to create stockable precursors, and more importantly, the exceptional radiosynthetic ease and the resulting high contrast images demonstrate that this method will be of potentially great utility to many applications.Research Support Genome BC, CIHR