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64Cu-Labeled Inhibitors of Prostate-Specific Membrane Antigen for PET Imaging of Prostate Cancer

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journal contribution
posted on 17.12.2015, 01:17 by Sangeeta Ray Banerjee, Mrudula Pullambhatla, Catherine A. Foss, Sridhar Nimmagadda, Riccardo Ferdani, Carolyn J. Anderson, Ronnie C. Mease, Martin G. Pomper
Prostate-specific membrane antigen (PSMA) is a well-recognized target for identification and therapy of a variety of cancers. Here we report five 64Cu-labeled inhibitors of PSMA, [64Cu]37, which are based on the lysine–glutamate urea scaffold and utilize a variety of macrocyclic chelators, namely NOTA­(3), PCTA­(4), Oxo-DO3A­(5), CB-TE2A­(6), and DOTA­(7), in an effort to determine which provides the most suitable pharmacokinetics for in vivo PET imaging. [64Cu]37 were prepared in high radiochemical yield (60–90%) and purity (>95%). Positron emission tomography (PET) imaging studies of [64Cu]37 revealed specific accumulation in PSMA-expressing xenografts (PSMA+ PC3 PIP) relative to isogenic control tumor (PSMA– PC3 flu) and background tissue. The favorable kinetics and high image contrast provided by CB-TE2A chelated [64Cu]6 suggest it as the most promising among the candidates tested. That could be due to the higher stability of [64Cu]­CB-TE2A as compared with [64Cu]­NOTA, [64Cu]­PCTA, [64Cu]­Oxo-DO3A, and [64Cu]­DOTA chelates in vivo.