Abstract
Purpose The purpose of this study was to develop 64Cu-labeled trastuzumab with improved pharmacokinetics for human epidermal growth factor receptor 2. Methods Trastuzumab was conjugated with SCN-Bn-NOTA and radiolabeled with 64Cu. Serum stability and immunoreactivity of 64Cu-NOTA-trastuzumab were tested. Small animal PET imaging and biodistribution study were performed in HER2-positive breast cancer xenograft model (BT-474). Internal dosimetry of experimental animals was performed using the image-based approach with the Monte Carlo N-Particle Code. Results 64Cu-NOTA-trastuzumab was prepared with high radiolabel yield and radiochemical purity (>98%) and showed high stability in serum and good immunoreactivity. Uptake of 64Cu-NOTA-trastuzumab was highest at 48 h after injection determined by PET imaging and biodistribution results in BT-474 tumors. The blood radioactivity concentrations of 64Cu-NOTA-trastuzumab decreased bi-exponentially with time in both mice with and without BT-474 tumor xenografts. The calculated absorbed dose of 64Cu-NOTA-trastuzumab was 0.048 mGy/MBq for the heart, 0.079 for the liver and 0.047 for the spleen. Conclusion 64Cu-NOTA-trastuzumab was effectively targeted to the HER2-expressing tumor in vitro and in vivo, and it exhibited relatively low absorbed dose due to short residence time. Therefore, 64Cu-NOTA-trastuzumab could be applied to select the right patients/right timing for HER2 therapy, to monitor the treatment response after HER2-targeted therapy, and to detect distal or metastatic spread.
- Monoclonal Antibodies
- Oncology: Breast
- Radioimmunoimaging
- <sup>64</sup>Cu-NOTA-trastuzumab
- Absorbed dose
- HER2
- Patient selection
- Treatment response
- Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.