HER-2-PET imaging with 89Zr-trastuzumab in metastatic breast cancer patients

Abstract

1045 Background: Non-invasive diagnostic tools can optimize and evaluate HER2 directed therapy in HER2 positive breast cancer patients. HER2 imaging with 111In-trastuzumab SPECT showed promising results (Perik et al, J Clin Oncol. 2006). To further optimize HER2 imaging, we developed 89Zr-trastuzumab for high resolution, quantitative and sensitive PET imaging. A feasibility study was performed to determine optimal conditions (tracer dose and scans) for visualization HER2 positive lesions. Methods: Trastuzumab was labeled with 89Zr according to Verel et al. (J Nucl Med. 2003). HER-2 positive metastatic breast cancer patients received 37 MBq 89Zr-trastuzumab at 3 protein doses of trastuzumab: 1) 10 mg, or 2) 50 mg trastuzumab, or 3) 10 mg trastuzumab when on trastuzumab treatment. Patients underwent 2 or 3 PET-scans during 1–7 days post tracer injection. Images were analyzed visually and the relative tissue or tumor uptake was calculated as the ratio tissue/tumor to whole body uptake. Results: Fourteen patients were included. Optimal time point to assess 89Zr-trastuzumab tumor uptake was 4–5 days post injection. The tracer dose of 10 mg was sufficient for patients on trastuzumab treatment, while best imaging results in trastuzumab naive patients were obtained with the 50 mg dose as 10 mg resulted in rapid tracer clearance. In trastuzumab naive patients, 89Zr-trastuzumab clearance was not only dose-dependent but also clearly influenced by tumor burden, indicating a need for individualization of therapy. 89Zr-trastuzumab PET-imaging detected not only known tumor lesions in the liver, lung, bone and brain but also unknown brain and bone lesions were detected. The mean relative tumor uptake(± SD) in liver, bone and brain lesions was respectively 13.0±5.2, 4.2±1.5 and 3.5±4.2, while mean relative tissue uptake in normal liver, spleen, kidneys and brain was respectively 6.1±2.3, 2.7±0.8, 3.8±1.0 and 0.19±0.11. Conclusions: HER2-PET imaging with 89Zr-trastuzumab shows excellent tumor tracer uptake and can be used to detect HER2 positive breast cancer metastases and to quantify 89Zr-trastuzumab uptake, non-invasively. Patients on trastuzumab can be imaged with 37 MBq 89Zr-trastuzumab at a protein dose of 10 mg trastuzumab while trastuzumab naive patients require 50 mg. No significant financial relationships to disclose.