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

• Published in: The Journal of nuclear medicine (1978) Vol. 59; no. 1; p. 38
• Main Authors: Mortimer, Joanne E, Bading, James R, Park, Jinha M, Frankel, Paul H, Carroll, Mary I, Tran, Tri T, Poku, Erasmus K, Rockne, Russell C, Raubitschek, Andrew A, Shively, John E, Colcher, David M
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01.01.2018
• Subjects: Biopsy; Breast cancer; Cancer; Clinical trials; Copper; Epidermal growth factor; ErbB-2 protein; Fluorescence; Fluorescence in situ hybridization; Immunoglobulins; Immunohistochemistry; Immunotherapy; Injection; Lesions; Metastases; Monoclonal antibodies; Patients; Positron emission tomography; Targeted cancer therapy; Trastuzumab; Variability
• ISSN: 0161-5505; 1535-5667

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). Methods: 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 SUVmax. Average intrapatient SUVmax (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 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 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 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.