Therapeutic effects of in-vivo radiodynamic therapy (RDT) for lung cancer treatment: a combination of 15MV photons and 5-aminolevulinic acid (5-ALA)

Abstract

Objective.Radiodynamic therapy (RDT) uses high-energy photon beams instead of visible/near-infrared light to treat deep-seated tumors that photodynamic therapy cannot achieve due to the low penetration depth of laser beams. The purpose of this study is to investigate the therapeutic effect of RDT with 15 MV photon beams combined with 5-aminolevulinic acid (5-ALA) using a mouse model.Approach.A subcutaneous C57BL/6 mouse model of KP1 small-cell lung cancer cell line was used. The tumors (N = 120) were randomized into four groups to observe individual and synergistic effects of 5-ALA and radiation treatment: control (untreated, N = 42), radiation treatment (RT) only (N = 20), 5-ALA only (N = 20), and RDT (N = 38). For the RT only and RDT groups, 4 Gy in a single fraction was delivered to the tumors using 15 MV photons. For the 5-ALA only and RDT groups, 5-ALA was injected at a dose of 100 mg kg^-1by tail-vein 4 h prior to RT. The tumor response was assessed by monitoring tumor growth using 1.5 T MR, maximum standardized uptake value (SUV_max) and total lesion glycolysis (TLG) using [¹⁸F]FDG PET/CT, and animal survival.Main results.RDT achieved a statistically significant delay in tumor growth by 52.1%, 48.1%, and 57.9% 7 days post-treatment compared to 5-ALA only, RT only, and control group (P < 0.001), respectively. There were no significant differences in tumor growth between 5-ALA only and RT only groups. An additional 38.5%-40.9% decrease in tumor growth was observed, showing a synergistic effect with RDT. Furthermore, RDT significantly decreased [¹⁸F]FDG uptakes in SUV_maxand TLG 7 days post-treatment by 47.4% and 66.5% (P < 0.001), respectively. RDT mice survived the longest of all treatment groups.Significance.RDT with 15 MV photons and 5-ALA resulted in greater tumor control compared to the control and other treatment groups. A significant synergistic effect was also observed with RDT. These preliminary results demonstrate an effective cancer treatment modality.

Keywords: 5-aminolevulinic acid (5-ALA); MRI; PET/CT; cancer treatment; radiodynamic therapy (RDT); therapeutic effect; tumor control.