Tumor Uptake of ⁶⁴Cu-DOTA-Trastuzumab in Patients with Metastatic Breast Cancer

Abstract

The goal of this study was to characterize the relationship between tumor uptake of ⁶⁴Cu-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). <b>Methods:</b> Women with biopsy-confirmed MBC and not given trastuzumab for 2 mo or more underwent complete staging, including ¹⁸F-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 ⁶⁴Cu-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 ⁶⁴Cu-DOTA-trastuzumab injection. Radiolabel uptake in prominent lesions was measured as SUV_max Average intrapatient SUV_max (<SUV_max>_pt) was compared between HER2+ and HER2- patients. <b>Results:</b> 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 <SUV_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 (<i>P</i> < 0.005 either day). The distributions of <SUV_max>_pt overlapped between the 2 groups, and interpatient variability was greater for HER2+ than HER2- disease (<i>P</i> < 0.005 and 0.001, respectively, on days 1 and 2). <b>Conclusion:</b> By 1 d after injection, uptake of ⁶⁴Cu-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 ⁶⁴Cu-DOTA-trastuzumab PET/CT in optimizing treatments that include trastuzumab.