A Modular Platform for the Rapid Site-Specific Radiolabeling of Proteins with 18F Exemplified by Quantitative Positron Emission Tomography of Human Epidermal Growth Factor Receptor 2

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• 作者：Herman S. Gill ; Jeff N. Tinianow ; Annie Ogasawara ; Judith E. Flores ; Alexander N. Vanderbilt ; Helga Raab ; Justin M. Scheer ; Richard Vandlen ; Simon-P. Williams ; Jan Marik
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：October 8, 2009
• 年：2009
• 卷：52
• 期：19
• 页码：5816-5825
• 全文大小：899K
• 年卷期：v.52,no.19(October 8, 2009)
• ISSN：1520-4804

文摘

Receptor-specific proteins produced by genetic engineering are attractive as PET imaging agents, but labeling with conventional ¹⁸F-based prosthetic groups is problematic due to long synthesis times, poor radiochemical yields, and low specific activities. Therefore, we developed a modular platform for the rapid preparation of water-soluble prosthetic groups capable of efficiently introducing ¹⁸F into proteins. The utility of this platform is demonstrated by the thiol-specific prosthetic group, [¹⁸F]FPEGMA, which was used to produce site-specifically ¹⁸F-labeled protein (¹⁸F-trastuzumab-ThioFab) in 82 min with a total radiochemical yield of 13 ± 3% and a specific activity of 2.2 ± 0.2 Ci/μmol. ¹⁸F-trastuzumab-ThioFab retained the biological activity of native protein and was successfully validated in vivo with microPET imaging of Her2 expression in a xenograft tumor-bearing murine model modulated by the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin.