Safety assessment, radioiodination and preclinical evaluation of antinuclear antibody as novel medication for prostate cancer in mouse xenograft model

Abstract

This study aims to provide in vitro and in vivo data to support the utilization of antinuclear antibodies (ANAs) as novel tools for the diagnosis and treatment of prostate cancers. The hematological, biochemical, and histological toxicities of ANAs were assessed at the doses of 5 and 50 μg per mouse. Radiolabeling study was then conducted with ANA and ¹³¹I using the chloramine T method, and the biodistribution and treatment efficacy were subsequently investigated in a PC3 xenograft model. No changes in clinical behavior or signs of intoxication, necrosis, or malignancy were observed in ANA-treated mice. ¹³¹I-ANA was obtained in very high yield and radiochemical purity, at 94.97 ± 0.98% and 98.56 ± 0.29%, respectively. They achieved immunoreactivity fraction of 0.841 ± 0.17% with PC-3 cells. Levels of radiolabeled ANAs were 1.15–10.14 times higher in tumor tissues than in other examined organs at 24 h post-injection. The tumor growth inhibition rates were 28.33 ± 5.01% in PC3 xenografts mice treated with ¹³¹I-ANAs compared with controls and a nearly twofold improvement in median survival was observed. These results demonstrate that radioimmunotherapy of radiolabeled natural ANAs may be an effective treatment for prostate tumors.