Abstract
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Objectives Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is widely used as treatment for HER2-positive breast cancer. The purpose of this study was to determine the distribution and pharmacokinetic characteristic of Cu-64-labeled trastuzumab in HER2-positive tumor xenografts mice model.
Methods Trastuzumab was conjugated with 2-S-(4-Isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bn-NOTA) and radiolabeled with Cu-64. Serum stability and immunoreactivity of Cu-64-NOTA-trastuzumab was tested. Small animal PET imaging and biodistribution study were performed in HER2-positive breast cancer (BT-474) xenografts at 6, 24, 48, and 72 h after i.v. injection of approximately 7.4 MBq of Cu-64-NOTA-trastuzumab. Also blood pharmacokinetic study was performed in both mice with and without BT-474 tumor xenograft.
Results Cu-64-NOTA-trastuzumab was prepared with high radiolabeling yield and showed high stability and good immunoreactivity. Cu-64-NOTA-trastuzumab was highly accumulated in HER2 positive tumor. Uptake of Cu-64-NOTA-trastuzumab was the maximum at 48 h after injection determined by PET images and biodistribution results. The blood radioactivity concentrations of Cu-64-NOTA-trastuzumab decreased bi-exponentially in both mice with and without BT-474 tumor xenograft.
Conclusions Trastuzumab can be efficiently radiolabelled with Cu-64 with high labeling yields and high stability. Cu-64-NOTA-trastuzumab was targeted to the HER2 both in vitro and in vivo. Therefore, NOTA conjugated trastuzumab could be applied for convergence radiopharmaceutical with Cu-64 (PET image radiopharmaceutical) or Cu-67 (therapeutic radiopharmaceutical).