Radiohalogenated Prostate-Specific Membrane Antigen (PSMA)-Based Ureas as Imaging Agents for Prostate Cancer

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• 作者：Ying Chen ; Catherine A. Foss ; Youngjoo Byun ; Sridhar Nimmagadda ; Mrudula Pullambhatla ; James J. Fox ; Mark Castanares ; Shawn E. Lupold ; John W. Babich ; Ronnie C. Mease ; Martin G. Pomper
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：December 25, 2008
• 年：2008
• 卷：51
• 期：24
• 页码：7933-7943
• 全文大小：341K
• 年卷期：v.51,no.24(December 25, 2008)
• ISSN：1520-4804

文摘

To extend our development of new imaging agents targeting the prostate-specific membrane antigen (PSMA), we have used the versatile intermediate 2-[3-(5-amino-1-carboxy-pentyl)-ureido]-pentanedioic acid (Lys-C(O)-Glu), which allows ready incorporation of radiohalogens for single photon emission computed tomography (SPECT) and positron emission tomography (PET). We prepared 2-[3-[1-carboxy-5-(4-[¹²⁵I]iodo-benzoylamino)-pentyl]-ureido]-pentanedioic acid ([¹²⁵I]3), 2-[3-[1-carboxy-5-(4-[¹⁸F]fluoro-benzoylamino)-pentyl]-ureido]-pentanedioic acid ([¹⁸F]6), and 2-(3-[1-carboxy-5-[(5-[¹²⁵I]iodo-pyridine-3-carbonyl)-amino]-pentyl]-ureido)-pentanedioic acid ([¹²⁵I]8) in 65−80% (nondecay-corrected), 30−35% (decay corrected), and 59−75% (nondecay-corrected) radiochemical yields. Compound [¹²⁵I]3 demonstrated 8.8 ± 4.7% injected dose per gram (%ID/g) within PSMA⁺ PC-3 PIP tumor at 30 min postinjection, which persisted, with clear delineation of the tumor by SPECT. Similar tumor uptake values at early time points were demonstrated for [¹⁸F]6 (using PET) and [¹²⁵I]8. Because of the many radiohalogenated moieties that can be attached via the ε amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer.