Assessment of early oxidative stress following the use of radiotheranostics agents 177Lu-PSMA for prostate cancer and 177Lu-DOTATATE for neuroendocrine tumors; radioprotective effect of vitamin C

Abstract

Background: We aimed first to evaluate the early oxidative stress following radionuclide therapy (RNT) with 177Lu-PSMA and 177Lu-DOTATATE and second to evaluate the protective effect of vitamin C on oxidative stress.

Materials and methods: Prostate cancer and neuroendocrine tumor (NET) patients referred to therapy with 177Lu-PSMA and 177Lu-DOTATATE, respectively, were enrolled in this study. The patients divided into the control group underwent routine RNT without any intervention and the intervention group was asked to take effervescent tablets (500 mg) of vitamin C for two days prior to the RNT (three tablets per day). To measure oxidative stress, blood samples were taken immediately before treatment and 48 h after treatment, and the serums were separated and frozen. To evaluate oxidative stress, the serum levels of malondialdehyde (MDA) and glutathione (GSH) and the activity of glutathione reductase were measured before and two days after treatment.

Results: In total, 61 RNT cycles were evaluated in 34 patients with age of 65 ± 2.83 (median ± SE) years (range of 27-99); this total included 20 (59%) prostate cancer patients [35 cycles (57.4%)] and 14 patients (41%) with NET [26 cycles (42.6%)]. Of the 61 evaluated cycles, 27 cycles were given in the control group and 34 cycles were given in the intervention group. The serum level of MDA was significantly increased after treatment compared to before treatment (P = 0.02) in the control group, while no significant change in the serum level of MDA was observed in the intervention group (P = 0.52). The serum level of GSH was insignificantly decreased after treatment compared to before treatment in the control group and slightly increased after treatment in the intervention group (P > 0.05). The serum level of glutathione reductase was insignificantly increased in all groups of patients after treatment (P > 0.05).

Conclusion: According to the results of this study, RNT with Lu-PSMA and Lu-DOTATATE may induce oxidative stress via the generation of free radicals and reactive oxygen species. Consumption of vitamin C prior to RNT may ameliorate this oxidative stress. These preliminary results have positive implications for clinical practice. Verification of these noteworthy results is needed and can be conducted with larger randomized controlled trials with longer time points.