Author: Lili Chen, Dusica Cvetkovic, Chang Ming Charlie Ma, Dae-Myoung Yang 👨🔬
Affiliation: Fox Chase Cancer Center 🌍
Purpose: 5-aminolevulinic acid (5-ALA)-mediated radiodynamic therapy (RDT) has been shown to be an effective treatment option using high-energy photon beams. RDT utilizes tumoricidal capabilities caused by both radiation and activated protoporphyrin IX, which is metabolized from 5-ALA. Cherenkov light induced by megavoltage photon beams effectively activates PpIX due to the Soret band. The emission of Cherenkov light increases with higher photon energy in water and ex-vivo tissues. Therefore, in need of using an in-vivo mouse model, this study aimed to investigate tumor response, photon efficacy, and normal tissue toxicity of megavoltage 5-ALA-mediated RDT.
Methods: The tumors (n=400) were randomized into eight groups: control (untreated), 5-ALA alone, radiation treatment (RT) alone, and RDT (RT with 5-ALA). 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, 15, and 45MV photons. 5-ALA was injected at 100mg/kg intravenously 4 hours before irradiation. Tumor volumes were measured using 1.5T MR, and normal tissue toxicity was assessed using the standard hematoxylin-eosin (H&E)-stained histopathologic score.
Results: 45MV RDT resulted in the most significant delay in tumor growth by 52.7±3.7%, 52.4±3.8%, and 47.6±4.2% compared to the control, 5-ALA alone, and 45MV RT alone on 14 days post-treatment, respectively (P<0.001). Compared to the different energies, 45MV RDT resulted in an additional 36.6±2.4% and 17.0±1.7% tumor growth delay compared to 6 and 15MV RDT 14-day post-treatment, respectively (P<0.001), whereas RT alone did not show significant differences. The histopathologic results showed no additional normal tissue damage from RDT compared to RT.
Conclusion: 5-ALA-mediated RDT resulted in significant tumor growth control and safe normal tissue responses, potentially leading to better patient outcomes. A photon energy dependency was observed in radiodynamic therapy, and higher photon energy beams activate PpIX more effectively.