Tumor uptake of 64 Cu-DOTA-trastuzumab in patients with metastatic breast cancer

Abstract

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 (HER21) or -negative (HER22) 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 (,SUV maxpt ) was compared between HER21 and HER22 patients. Results: Eleven women were HER21 (8 immunohistochemistry 31; 3 immunohistochemistry 21/FISH amplified), whereas 7 were HER22 (3 immunohistochemistry 21/FISH nonamplified; 4 immunohistochemistry 11). Median,SUV maxpt for day 1 and day 2 was 6.6 and 6.8 g/mL for HER 21 and 3.7 and 4.3 g/mL for HER22 patients (P, 0.005 either day). The distributions of,SUV maxpt overlapped between the 2 groups, and interpatient variability was greater for HER21 than HER22 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 HER21 patients, as well as the overlap between the HER21 and HER22 groups, suggests a role for 64 Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab.