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

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• 作者：Sangeeta Ray Banerjee ; Mrudula Pullambhatla ; Catherine A. Foss ; Sridhar Nimmagadda ; Riccardo Ferdani ; Carolyn J. Anderson ; Ronnie C. Mease ; Martin G. Pomper
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：March 27, 2014
• 年：2014
• 卷：57
• 期：6
• 页码：2657-2669
• 全文大小：515K
• 年卷期：v.57,no.6(March 27, 2014)
• ISSN：1520-4804

文摘

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]3鈥?b>7, which are based on the lysine鈥揼lutamate 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]3鈥?b>7 were prepared in high radiochemical yield (60鈥?0%) and purity (>95%). Positron emission tomography (PET) imaging studies of [⁶⁴Cu]3鈥?b>7 revealed specific accumulation in PSMA-expressing xenografts (PSMA+ PC3 PIP) relative to isogenic control tumor (PSMA鈥?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.