Synthesis and Evaluation of Technetium-99m- and Rhenium-Labeled Inhibitors of the Prostate-Specific Membrane Antigen (PSMA).
作者
Banerjee, Sangeeta R.;Foss, Catherine A.;Castanares, Mark;Mease, Ronnie C.;Byun, Youngjoo;Fox, James J.;Hilton, John;Lupold, Shawn E.;Kozikowski, Alan P.;Pomper, Martin G.;
[摘要]：The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. We prepd. seven 99mTc/Re-labeled compds. by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor (lys-NHCONH-glu) with or without a variable length linker moiety. Ki values ranged from 0.17 to 199 nM. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors. PC3-PIP cells are derived from PC3 that have been transduced with the gene for PSMA. Despite demonstrating nearly the lowest PSMA inhibitory potency of this series, [99mTc(CO)3(L1)]+ (L1 = (2-pyridylmethyl)2N(CH2)4CH(CO2H)NHCO-(CH2)6CO-NH-lys-NHCON H-glu) showed the highest, most selective PIP tumor uptake, at 7.9 ? 4.0% injected dose per g of tissue at 30 min postinjection. Radioactivity cleared from nontarget tissues to produce a PIP to flu (PSMA-PC3) ratio of 44:1 at 120 min postinjection. PSMA can accommodate the steric requirements of 99mTc/Re complexes within PSMA inhibitors, the best results achieved with a linker moiety between the e amine of the urea lysine and the chelator.
