Cell binding and toxicity studies of ¹⁷⁷Lu- labeled trastuzumab

Trastuzumab, a humanized monoclonal antibody (mAb) specific for the HER2 receptor, is approved for the immunotherapy of metastatic breast cancer. The aim here was to study the cell binding and toxicity of the in-house developed ¹⁷⁷Lu- trastuzumab formulation in HER2 positive breast cancer cell lines. Trastuzumab was conjugated to p-SCN-benzyl-CHX- A"-DTPA and radiolabeled with ¹⁷⁷Lu. Cell binding studies carried out in MDA-MB 453 cells showed a maximum binding of 9.3 ± 0.3% which decreased to 1.9 ± 0.1% (∼80% inhibition) when co-incubated with excess of unlabeled trastuzumab indicating the specificity of ¹⁷⁷Lu-CHX-A"-DTPA-Trastuzumab to HER2 positive cells. Toxicity and cell viability studies were assessed by LDH assay and Flow cytometry respectively. In LDH assay, approximately 15% more cell death was observed in HER2 positive cells which were treated with 37 MBq of ¹⁷⁷Lu- Trastuzumab as compared to the control. Evaluation of cell viability by flow cytometry showed 8% more toxicity when exposed to ¹⁷⁷Lu- Trastuzumab as compared to Trastuzumab alone. These studies indicate the potential of ¹⁷⁷Lu- Trastuzumab in inducing cell death to HER2 positive breast cancer cells and its utility in cancer radioimmunotherapy. (author)