Low dose hyper-radiosensitivity as an intervention strategy to enhance ¹⁷⁷Lu-iPSMA treatment in LNCaP cells

Low dose induced hyper-radiosensitivity refers to the acquired sensitivity to ionizing radiation due to the exposure to radiation doses <1Gy. Therefore, the aim of the present study was to evaluate whether induction of the hyper-radiosensitivity phenomenon in prostate cancer cells could improve the outcome of ¹⁷⁷Lu-iPSMA therapy. Reduction in viability, loss of clonal expansion capacity and decrease of LNCaP prostate cancer cells survival by the promotion of cell apoptosis, is enhanced by gamma irradiation at doses of less than 1 Gy (⁶⁰Co Gammacell 220 system, 0.24 Gy/min) prior to administration of the targeted radiopharmaceutical. Analysis of survival curves, showed that 0.50 Gy is the predose that improved the TRT therapeutic effect. Pre-irradiation significantly reduced the LNCaP α⁄β ratio from 4.65 to 1.38 in LNCaP cells that received a¹⁷⁷Lu-iPSMA absorbed radiation dose to the nucleus between 2 and 10 Gy.