Functional imaging of HER2-positive metastatic breast cancer using 64Cu DOTA-trastuzumab positron emission tomography (PET).

Abstract

639 Background: We are developing 64Cu-labeled trastuzumab (tras) as a PET imaging agent for women with HER2+ beast cancer. To maximize image quality and minimize HER2 uptake in normal tissues, we pre-administered 2 different doses of cold tras prior to injection of the imaging agent. Methods: Pts with advanced breast cancer were eligible if they had bx confirmed HER2 + disease, had not received anti-HER therapy for 6 mos. and had > 1 non-hepatic site of metastasis > 2 cm outside the biopsy site. All un-derwent staging FDG/PET and bone scan. Prior to injection of 64Cu-tras, pts. received 5 or 50 mg (2 and 4 pts) of cold tras. PET-CT was obtained at 21-25 h and 47-48 h over fields of view chosen in reference to 18F-FDG scans. Uptake in organs and lesions were measured in terms of body wt-normalized SUV. Lesions with intensity > adjacent tissue were considered positive on PET. The number of metastatic sites identified on 64Cu-tras/PET was compared to the number on FDG/PET. Image quality was assessed according to differences between the 2 pretreatment doses. Results: Six pts have been imaged. Tras dose had a marked effect on liver uptake of64Cu [SUV = 23±3 (mean±sd) and 6.3±0.6 for 5 and 50 mg tras, respectively; P < 0.05]. 72 CT+ lesions (32 bone, 28 nodal, 9 liver, 2 breast, 1 lung) were included in D1 and/or D2 scans. Of these, 66 of 72 (92%), 48 of 63 (76%) and 36 of 44 (82%) were detected on FDG, D1 and D2 scans, respectively. Lesion SUVmax was 9±5 (n=37, range 3-23) on D1 and 11±6 (n=27, range 1-29) on Day 2. 64Cu-tras-to-FDG SUVmax ratios were 1.0±0.8 (range 0.2-4.3) and 1.3±1.1 (range 0.2-3.5) for D 1 and 2. Lesion 64Cuuptake trendedliver > bone > nodes. Conclusions: 64Cu-tras/PET visualizes HER2+ lesions in bone, liver and, to a lesser degree, lymph nodes. Pre-administration of cold tras improves the quality of tras/PET, especially of intrahepatic lesions. In the next phase of study we will perform 64Cu-tras/PET in pts with HER2 1+ and 2+ disease.