Abstract P2-05-10: 64Cu-DOTA-trastuzumab positron emission tomography imaging of HER2 in women with advanced breast cancer

Abstract

Abstract Background: We propose to utilize64Cu-DOTA-trastuzumab with PET imaging to assess the in vivo expression of HER2 in women with advanced breast cancer. We hypothesized that the uptake of HER2 in normal tissues compromises the quality of radiographic images and that the pre-administration of trastuzumab prior to injection of64Cu-DOTA-trastuzumab would improve image quality. Two different doses of cold trastuzumab (5 mg and 50 mg) were tested. Once the dose of cold trastuzumab was established in women with documented HER2 positive metastatic disease, we initiated a second study of64Cu-DOTA-trastuzumab PET imaging in women whose cancers were HER2 1+ and 2+ by immunohistochemical staining. Methods: Patients with biopsy confirmation of recurrent disease located outside the breast and axilla considered for study. Complete staging workup included CT of the chest, abdomen, and pelvis, bone scintigraphy and18F FDG PET. At lease 1 non-hepatic site of metastasis that was > 2 cm separate from the biopsy site was also required. HER2 status was assessed by both IHC and FISH. In the first study all patients were required to have HER2 positive disease and could not have received anti-HER therapy for > 2 months. Immediately prior to injection of64Cu-DOTA-trastuzumab, a cold dose of either 5 mg or 50 mg of trastuzumab was administered.64Cu-DOTA-trastuzumab PET imaging was performed at 24 and 48 hours. Results: Eight women with HER2 positive metastatic breast cancer have undergone64Cu-DOTA-trastuzumab PET imaging: 2 received a pre-64Cu-DOTA-trastuzumab PET dose of 5 mg trastuzumab and 6 received 50 mg.64Cu-DOTA-trastuzumab PET effectively visualized and provided uptake measurements for presumably HER2+ metastatic lesions in bone, liver, lung and, to a lesser degree, lymph nodes. The 50 mg dose resulted in approximately 75% decrease in liver uptake of64Cu and improved the visualization of hepatic metastasis. We have initiated the second phase of the study utilizing the pre-administration of 50 mg trastuzumab in women with HER2 1+ and 2 + disease. To date we have imaged one patient. Conclusion:64Cu-DOTA-trastuzumab PET imaging is feasible and image quality is improved with the pre-administration of 50 mg trastuzumab. Enrollment of women with IHC 1+ and 2+ disease continues. This work was supported by the Department of Defense grant # 1024511. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-10.