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We hypothesized that functional imaging with 64 Cu-DOTA-trastuzumab PET/CT would predict the response to the antibody-drug conjugate trastuzumab-emtansine (T-DM1). Methods: Ten women with metastatic human epidermal growth factor receptor 2-positive breast cancer underwent 18 F-FDG PET/CT and 64 Cu-DOTA-trastuzumab PET/CT on days 1 and 2 before treatment with T-DM1. Results: T-DM1-responsive patients had higher uptake than nonresponsive patients. Day 1 minimum SUV max (5.6 vs. 2.8, P < 0.02), day 2 minimum SUV max (8.1 vs. 3.2, P < 0.01), and day 2 average SUV max (8.5 vs. 5.4, P < 0.05) for 64 Cu-DOTA-trastuzumab all favored responding patients. Tumor-level response suggested threshold dependence on SUV max Patients with a day 2 minimum SUV max above versus below the threshold had a median time to treatment failure of 28 mo versus 2 mo ( P < 0.02). Conclusion: Measurement of trastuzumab uptake in tumors via PET/CT is promising for identifying patients with metastatic breast cancer who will benefit from T-DM1., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

The goal of this study was to characterize the relationship between tumor uptake of 64 Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Methods: Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, including 18 F-FDG PET/CT. Patients were classified as HER2-positive (HER2+) or -negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented immunohistochemistry of biopsied tumor tissue. Eighteen patients underwent 64 Cu-DOTA-trastuzumab injection, preceded in 16 cases by trastuzumab infusion (45 mg). PET/CT was performed 21-25 (day 1) and 47-49 (day 2) h after 64 Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUV max Average intrapatient SUV max (max > pt ) was compared between HER2+ and HER2- patients. Results: Eleven women were HER2+ (8 immunohistochemistry 3+; 3 immunohistochemistry 2+/FISH amplified), whereas 7 were HER2- (3 immunohistochemistry 2+/FISH nonamplified; 4 immunohistochemistry 1+). Median max > pt for day 1 and day 2 was 6.6 and 6.8 g/mL for HER 2+ and 3.7 and 4.3 g/mL for HER2- patients ( P < 0.005 either day). The distributions of max > pt overlapped between the 2 groups, and interpatient variability was greater for HER2+ than HER2- disease ( P < 0.005 and 0.001, respectively, on days 1 and 2). Conclusion: By 1 d after injection, uptake of 64 Cu-DOTA-trastuzumab in MBC is strongly associated with patient HER2 status and is indicative of binding to HER2. The variability within and among HER2+ patients, as well as the overlap between the HER2+ and HER2- groups, suggests a role for 64 Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)