Small-Animal PET Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with Site-Specific 18F-Labeled Protein Scaffold Molecules

Human epidermal growth factor receptor type 2 (HER2) is a well-established tumor biomarker that is overexpressed in a wide variety of cancers and that serves as a molecular target for ther-apeutic intervention. HER2 also serves as a prognostic indicator of patient survival and as a predictive marker of the response to antineoplastic therapy. The development of 18F-labeled bio-molecules for PET imaging of HER2 (HER2PET) is very important because it may provide a powerful tool for the early detection of HER2-positive tumor recurrence and for themonitoring of HER2-based tumor treatment.Methods: In this study, anti-HER2mono-meric and dimeric protein scaffold molecules [ZHER2:477 and (ZHER2:477)2, respectively] were radiofluorinated at a reasonable radiochemical yield (13%–18%) by use of site-specific oxime chemistry. The resulting radiofluorinated protein scaffold mole-cules were then evaluated as potential molecular probes fo