Radiodynamic therapy using 15-MV radiation combined with 5-aminolevulinic acid and carbamide peroxide for prostate cancer in vivo

Abstract

Photodynamic therapy has been clinically proven to be effective, but its effect is limited to relatively shallow tumors because of its use of visible light. Radiodynamic therapy (RDT) has therefore been investigated as a means to treat deep-seated tumors. In this study, the treatment effect of a novel form of RDT consisting of radiation combined with 5-aminolevulinic acid (5-ALA) and carbamide peroxide was investigated using a mouse model. Male nude mice were injected bilaterally and subcutaneously with human prostate cancer (PC-3) cells and randomized into 8 treatment groups, consisting of various combinations of 15-MV radiotherapy (RT), 5-ALA, and carbamide peroxide. The treatment effect of a single fraction of treatment was measured by calculating tumor growth delay, monitored using weekly MR scans. The ability of the drugs to be delivered to the tumors was qualitatively measured using 18 F-FDG PET/CT scans. RDT was shown to significantly delay the tumor growth for the mouse model and tumor cell line investigated in this work. Tumors treated with RDT showed a decrease in tumor growth of 24 ± 9% and 21 ± 8% at one and two weeks post-treatment, respectively. Peroxide and 5-ALA did not contribute significantly to tumor growth delay when administered alone or separately with RT. Blood perfusion was shown to be able to deliver agents to the tumors investigated in this work, although uptake of 18 F-FDG was shown to be non-uniform.