Cellular Uptake and Computational Analysis of [¹³¹I]-Xanthine and [¹³¹I]-Hypoxanthine in Human Prostate Cancer Cell Line (LNCaP)

Potent radiolabelled compounds eligible for therapy of prostate cancer need to be developed. Hence, we developed two candidate therapeutic agents bearing the iodine-131 (131I) radionuclide, namely, [131I]-xanthine (3,7-dihydropurine-2,6-dione) and [131I]-hypoxanthine (1,9-dihydro-6H-purin-6-one). The radiolabelled compounds were subjected to a cellular uptake study, which was accomplished by incubating [131I]-xanthine and [131I]-hypoxanthine with the human prostate cancer cell line (LNCaP) for 5, 15, 30, 60, and 90 min. Results showed that the accumulation of both [131I]-xanthine and [131I]-hypoxanthine in prostate cancer cells was significantly higher than the control group (131I). [131I]-xanthine rapidly accumulated in prostate cancer cells, with the highest percentage of cellular uptake of 2.73% ± 0.40% observed at 30 min of incubation. By contrast, [131I]-hypoxanthine exhibited more efficient accumulation in prostate cancer cells, especially at 60 and 90 min of incubation, with cellular uptake values of 11.5% ± 3.14% and 11.9% ± 1.83%, respectively. Furthermore, the computational analysis showed that radioiodinated xanthine and hypoxanthine provide potential binding affinities and interaction on both androgen and prostate-specific membrane antigen receptors. Overall, this study indicates that [131I]-xanthine and [131I]-hypoxanthine can be potentially developed as therapeutic agents for prostate cancer.