Figure 1d:

Identification of human epidermal growth factor receptor 2 (HER2)-positive metastases in a 66-year-old woman with HER2-negative primary breast cancer by using HER2-targeted zirconium 89 (⁸⁹Zr)-pertuzumab PET/CT. (a) HER2 immunohistochemistry of the primary breast malignancy at 200× magnification was 1+ (faint staining, arrow), consistent with HER2-negative malignancy. (b) Maximum intensity projection image from research ⁸⁹Zr-pertuzumab PET/CT demonstrates multiple osseous and hepatic foci, suspicious for HER2-positive malignancy (arrows show hepatic [standardized uptake value, 18.1] and osseous [standardized uptake value, 16.5] reference lesions). (c) Axial CT image in patient in prone position acquired from a CT-guided biopsy of an ⁸⁹Zr-pertuzumab–avid osseous focus. (d) HER2 immunohistochemistry at 200× magnification of the biopsied lesion was 2+ (moderate staining, arrow); 2+ HER2 immunohistochemistry is considered equivocal and thus HER2 fluorescence in situ hybridization (FISH) was performed. (e) HE (CEP17) copy number 3.07, and HER2/CEP17 ratio of 3.0, consistent with HER2-positive disease. Given the new diagnosis of HER2-positive metastases, the woman began treatment with docetaxel, trastuzumab, and pertuzumab. (f) Maximum intensity projection image from fluorodeoxyglucose PET/CT performed before initiation of therapy and (g) after 2 months of therapy demonstrate a substantial partial response (arrows in f and g indicate hepatic [standardized uptake value, 4.5 before therapy, standardized uptake value equal to background after therapy] and osseous [standardized uptake value, 8.4 before therapy, standardized uptake value equal to background after therapy] reference lesions).