Comparative cytotoxicity of Lu-177 on various lung cancer cells and in vivo targeting of Lu-177-labeled cetuximab

Differences in cellular radiosensitivity and the binding affinity of radiopharmaceuticals could directly affect the radiotherapeutic effects. In this study, we investigated the radionuclide (Lu-177) induced radiosensitivity of serval non-small-cell lung cancer cells (NSCLCs) as well as the binding affinity of cetuximab to those cells. The apoptosis of NSCLCs caused by Lu-177 was related to the DNA double-strand damage and was cell-type dependent. We also proved that the introduction of Lu-177 to the antibody could enhance its cytotoxic effect on NSCLCs. The [Lu-177]Lu-DOTA-cetuximab could accumulate in the HCC827 tumor xenografts with excellent stability according to in vivo SPECT/CT imaging and the biodistribution results. The [Lu-177]Lu-DOTA-cetuximab showed high potential to be used for targeting diagnosis and radiotherapy in lung cancers.

Automated summary

This study investigated the radiosensitivity induced by Lu-177 and the binding affinity of cetuximab to several non-small-cell lung cancer cells (NSCLCs). Lu-177 caused apoptosis in NSCLCs through DNA double-strand damage, which was dependent on cell type. Introducing Lu-177 to the antibody enhanced its cytotoxic effect on NSCLCs. The [Lu-177]Lu-DOTA-cetuximab showed great potential for targeting diagnosis and radiotherapy in lung cancers, as demonstrated by in vivo SPECT/CT imaging and biodistribution results.