Radiosensitivity of Prostate Cancer Cell Lines for Irradiation from Beta Particle-emitting Radionuclide 177Lu Compared to Alpha Particles and Gamma Rays

Aim: The purpose of the present study was to investigate the radiosensitivity of the prostate cancer cell lines LNCaP, DU145, and PC3 when irradiated with beta particles emitted from Lu-177, and to compare the effect with irradiation using alpha particles or gamma rays. Materials and Methods: Cells were irradiated with beta particles emitted from Lu-177, alpha particles from Am-241, or gamma rays from Cs-137. A nonspecific polyclonal antibody was labeled with Lu-177 and used to irradiate cells in suspension with beta particles. A previously described in-house developed alpha-particle irradiator based on a Am-241 source was used to irradiate cells with alpha particles. External gamma-ray irradiation was achieved using a standard Cs-137 irradiator. Cells were irradiated to absorbed doses equal to 0, 0.5, 1, 2, 4, 6, 8, or 10 Gy. The absorbed doses were calculated as mean absorbed doses. For evaluation of cell survival, the tetrazolium-based WST-1 assay was used. After irradiation, WST-1 was added to the cell solutions, incubated, and then measured for level of absorbance at 450 nm, indicating the live and viable cells. Results: LNCaP, DU145, and PC3 cell lines all had similar patterns of survival for the different radiation types. No significant difference in surviving fractions were observed between cells treated with beta-particle and gamma-ray irradiation, represented for example by the surviving fraction values (mean +/- SD) at 2, 6, and 10 Gy (SF2, SF6, and SF10) for DU145 after beta-particle irradiation: 0.700 +/- 0.090, 0.186 +/- 0.050 and 0.056 +/- 0.010, respectively. A strong radiosensitivity to alpha particles was observed, with SF2 values of 0.048 +/- 0.008, 0.018 +/- 0.006 and 0.015 +/- 0.005 for LNCaP, DU145, and PC3, respectively. Conclusion: The surviving fractions after irradiation using beta particles or gamma rays did not differ significantly at the absorbed dose levels and dose rates used. Irradiation using alpha particles led to a high level of cell killing. The results show that the beta-particle emitter Lu-177 as well as alpha-particles are both good candidates for radionuclide-therapy applications in the treatment of prostate cancer.