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

Article abstract of DOI:10.1021/jm900420c

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. 2009 American Chemical Society.