PET of HER2-positive pulmonary metastases with ¹⁸F-Z _HER2:342 affibody in a murine model of breast cancer: Comparison with ¹⁸F-FDG

Targeted therapies often depend on the expression of the target present in the tumor. This expression can be difficult to ascertain in widespread metastases. ¹⁸F-FDG PET/CT, although sensitive, is nonspecific for particular tumor markers. Here, we compare the use of a human epidermal growth factor receptor 2 (HER2)-specific ¹⁸F-Z _HER2:342-Affibody and ¹⁸F-FDG in HER2-expressing pulmonary metastases in a murine model of breast cancer. Methods: The lung metastasis model was established by intravenous injection of MDA-MB-231 _HER2-Luc human breast cancer cells into the tail vein. Bioluminescence imaging was used to evaluate metastasis progression. Uptake of ¹⁸F-Z _HER2:342-Affibody and ¹⁸F-FDG was confirmed by coregistration of the PET images with MR and CT images. At the end of the study, the presence of neoplastic cells and HER2 expression in lung tissues, and distribution of the tracer, were assessed ex vivo by immunohistochemistry and autoradiography. Results: ¹⁸F-Z _HER2:342-Affibody successfully targeted HER2-positive lesions in the lung and allowed detection of metastases as early as 9 wk after injection of cells. In contrast, ¹⁸F-FDG uptake was often masked by surrounding inflammatory changes and was nonspecific for HER2 expression. HER2 expression at a cellular level correlated well with tracer uptake on autoradiography. Conclusion: ¹⁸F-Z _HER2:342-Affibody is a promising tracer for evaluation of HER2 status of breast cancer metastases and is more specific for detecting HER2-positive lesions than ¹⁸F-FDG.