Author: Lili Chen, Dusica Cvetkovic, Chang Ming Charlie Ma, Dae-Myoung Yang 👨🔬
Affiliation: Fox Chase Cancer Center 🌍
Purpose: Cytotoxicity caused by the reactive oxygen species (ROS) is a mechanism for treating cancer cells in radiation therapy. 5-aminolevulinic acid (5-ALA)-mediated radiodynamic therapy (RDT), which combines the principles of radiotherapy and photodynamic therapy (PDT) is more tumoricidal than conventional radiation therapy. ROS is produced not only by ionizing radiation but also by Cherenkov light-activated protoporphyrin IX (PpIX), which is metabolized from 5-ALA. Moreover, PpIX in X-ray irradiation in-vitro catalyzes carbamide peroxide (PRX) to generate ROS, which enhances catalytic yield of ROS. Therefore, in need of using an in-vivo mouse model, this study aimed to investigate the effect of carbamide peroxide as a coenzyme catalyst on a megavoltage 5-ALA-mediated RDT.
Methods: The tumors (n=200) were randomized into ten groups: control (untreated), 5-ALA alone, PRX alone, 5-ALA with PRX, RDT (RT with 5-ALA) with or without PRX using 6, 18, and 45MV photons. A radiation dose of 4Gy in a single fraction was delivered using half-body irradiation to the tumors and lower parts of the body using 6, 18, and 45MV photons. 5-ALA was injected at 100mg/kg intravenously 4 hours before irradiation. Carbamide peroxide was injected at 60 mg/kg intratumorally into tumors ~3-5 minutes before the treatment. Tumor volumes were measured using 1.5T MR.
Results: 45MV RDT with PRX resulted in the most significant delay in tumor growth by 58.8 ± 8.0% and 14.6 ± 1.8% compared to the control and 45MV RDT without PRX on 14 days post-treatment, respectively. The enhancement effect of carbamide peroxide on RDT was shown to be effective after 7 days post-treatment.
Conclusion: The catalytic effect of PpIX and carbamide peroxide was observed in-vivo 5-ALA RDT. The enhancement results suggest that the additional ROS produced by PRX prolongs the tumor growth delay.