RT Journal Article SR Electronic T1 Small-Animal PET Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with Site-Specific 18F-Labeled Protein Scaffold Molecules JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 804 OP 813 DO 10.2967/jnumed.107.047381 VO 49 IS 5 A1 Zhen Cheng A1 Omayra Padilla De Jesus A1 Mohammad Namavari A1 Abhijit De A1 Jelena Levi A1 Jack Matt Webster A1 Rong Zhang A1 Brian Lee A1 Faisal A. Syud A1 Sanjiv Sam Gambhir YR 2008 UL http://jnm.snmjournals.org/content/49/5/804.abstract AB 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 therapeutic 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 biomolecules for PET imaging of HER2 (HER2 PET) is very important because it may provide a powerful tool for the early detection of HER2-positive tumor recurrence and for the monitoring of HER2-based tumor treatment. Methods: In this study, anti-HER2 monomeric 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 molecules were then evaluated as potential molecular probes for small-animal HER2 PET by use of a SKOV3 tumor–bearing mouse model. Results: The 4-18F-fluorobenzaldehyde conjugated aminooxy-protein scaffolds [18F-N-(4-fluorobenzylidene)oxime (FBO)-ZHER2:477 and 18F-FBO-(ZHER2:477)2] both displayed specific HER2-binding ability in vitro. Biodistribution and small-animal PET imaging studies further revealed that 18F-FBO-ZHER2:477 showed rapid and high SKOV3 tumor accumulation and quick clearance from normal tissues, whereas 18F-FBO-(ZHER2:477)2 showed poor in vivo performance (low tumor uptake and tumor-to-normal tissue ratios). The specificity of 18F-FBO-ZHER2:477 for SKOV3 tumors was confirmed by its lower uptake on pretreatment of tumor-bearing mice with the HER2-targeting agents ZHER2 and trastuzumab. Moreover, small-animal PET imaging studies revealed that 18F-FBO-ZHER2:477 produced higher-quality tumor imaging than 18F-FBO-(ZHER2:477)2. 18F-FBO-ZHER2:477 could clearly identify HER2-positive tumors with good contrast. Conclusion: Overall, these data demonstrate that 18F-FBO-ZHER2:477 is a promising PET probe for imaging HER2 expression in living mice. It has a high potential for translation to clinical applications. The radiofluorination method developed can also be used as a general strategy for the site-specific labeling of other proteins with 18F. The protein scaffold molecules used here are attractive for the further development of PET probes for other molecular targets.