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

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.