Abstract
1055
Objectives: In present study, we evaluate the HER2-targeting ability and therapeutic potential of 177Lu-labeled Herceptin in lung cancer animal model.
Methods: Herceptin was labeled with lutetium-177 using DOTA as chelator. The radiochemical purity and the in vitro stability of 177Lu-DOTA-Herceptin were determined using HPLC. 177Lu-DOTA-Herceptin was injected intravenously into mice bearing lung cancer xenografts, which were established using SPCA-1 human lung adenocarcinoma cell, and SPECT/CT imaging was performed at 2, 4, 12, 24, 48, 72, 96 h after injection. The status of HER2 expression in tumor was detected by immunohistochemical analysis. The binding specificity of radiotracer and HER2 in vivo was assessed by the the pretreatment with an excess of unlabeled Herceptin. The treatment effect of 177Lu-DOTA-Herceptin was evaluated by measuring the tumor size at day 3, 7, 10 after injection.
Results: After purification, the radiochemical purity of 177Lu-DOTA-Herceptin was 95.6%, and the stabilities in PBS and human blood serum at 48 h post-preparation were 91.5% and 87.2%, respectively. The immunohistochemistry result confirmed the HER2 overexpression in lung cancer animal model. SPECT/CT images showed that the radiotracer accumulation in tumor site occurred from 4 h to 72 h, and the maximum uptake was at 48 h time point, which can be blocked significantly by pretreatment with Herceptin, demonstrating the tracer can recognize and bind HER2 specifically. Compared with the control group, an inhibition effect of tumor growth was observed after the injection of 177Lu-DOTA-Herceptin.
Conclusions: 177Lu-DOTA-Herceptin can be considered for further evaluations as a potential theranostic agent for HER2-positive lung cancer.