Introduction: Prostate Specific Membrane Antigen (PSMA) is highly expressed on the surface of prostate carcinomas. Previously, we demonstrated successful PET imaging of PSMA-expressing xenografts using the urea-based PSMA inhibitors [ 11 C]DCMC (Clin Cancer Res 2005; 11:1022), and [ 18 F]DCFBC (J Nucl Med 2006; 47:89P). Recently, we and others have shown that large substituents can be attached to an amino analog, by use of a suitable linker moiety (Mol Imaging 2006; 5:322; Chem Med Chem 2006; 1:299). Using this approach we now report the synthesis of [Re/ 99m Tc]tricarbonyl-bisquinoline compounds 5a,b, and -bispyridyl compounds 6a,b, and their biodistribution in mice harboring PSMA+ and PSMA-tumors.
Experimental: Syntheses of 5a,b and 6a,b are shown in Figure 1. Radiochemical yields were 71% and 82%, and the radiochemical purities were 96.0% and 98.8% for 5b and 6b respectively. SCID mice bearing a PSMA+PC-3 Pip tumor and a PSMA-PC-3 Flu tumor on either shoulder were injected via the tail vein with 50ΞΌCi of 5b or 6b. Mice (4 per time point) were sacrificed at various time points. Tumor, blood, and major organs were harvested, weighed, and radioactivity was counted.
Results and Discussion: Compounds 5b and 6b showed specific uptake in PSMA+ tumors. At 0.5 and 1 hr PC-3 Pip tumor uptake of 5b was 1.1Β±0.6 and 2.0Β±0.3%ID/g respectively. Compound 5b exhibited high uptake within spleen, kidney, and small intestine. TumorT/blood (B), T/liver(L), T/spleen(Spl), T/kidney(K), T/small intest(SI), T/Large Intest(LI), and T/bladder(Bldr) ratios were 4, 0.6, 0.1, 0.02, 0.2, 1, and 2 at 0.5 hr and 6, 2, 0.1, 0.02, 1, 4, and 5 at 1 hr. Compound 6b had PC-3 Pip tumor uptake of 7.9Β±4, 3.9Β±0.6, 2.3Β±0.8, and 0.8Β±0.5%ID/g at 0.5, 1, 2, amd 5 hr respectively. Compound 6b exhibited rapid blood clearance with high initial Spl, K, and SI uptake.