Evaluating Therapeutic Effects of In Vivo 15MV Radiodynamic Therapy (RDT) with 5-Aminolevulinic Acid (5-ALA) Using 1.5T MRI and [18F]FDG PET/CT

Abstract

<h3>Purpose/Objective(s)</h3> A combination of photosensitizer and high-energy photon beam is required to perform radiodynamic therapy (RDT) for tumor treatment. High-energy photon beams activate the photosensitizer, leading to cellular toxicity by producing extra reactive oxygen species to kill malignant cells. The purpose of this study was to investigate the therapeutic effect of RDT with 15 MV photon beams combined with 5-aminolevulinic acid (5-ALA) using a mouse model. <h3>Materials/Methods</h3> All animal studies were approved by our Institutional Animal Care and Use Committee. A subcutaneous murine KP1 small-cell lung cancer model using C57BL/6 mice was used. The tumors (n=126) were randomly assigned into four groups, including control (untreated), radiation treatment (RT) only, 5-ALA only, and RDT to observe individual and synergistic effects of 5-ALA and radiation treatment. Treatment was performed when the tumor reached 5-8 mm in diameter. A single fraction of 4 Gy was delivered to the tumors using 15 MV photons on a clinical linear accelerator for RT only and RDT groups. 5-ALA was injected at 100 mg/kg by tail-vein 4 hours prior to RT for 5-ALA only and RDT groups. Tumor volumes were measured using a 1.5 T MR scanner on the day of treatment and weekly post-treatment. Tumor growth for each tumor was quantified as the ratio of tumor volume one- and two-week post-treatment to the tumor volume on the treatment day. SUV_max and total lesion glycolysis (TLG) were measured using [¹⁸F]FDG PET/CT for control and RDT groups. A 10 min static scan was acquired an hour after an injection of 80 µCi [¹⁸F]FDG. SUV_max was calculated as the maximum measured activity concentration divided by the injected whole bodyweight activity concentration. TLG was quantified as a product of SUV_mean and the metabolic tumor volume. <h3>Results</h3> The tumor growth in the RDT group was delayed by 48.3±11.3%, 46.3±9.2%, and 54.6±12.7% at one-week post-treatment compared to 5-ALA only, RT only, and the control group (P<0.001), respectively. There were no significant differences in tumor growth between 5-ALA only, RT only, and the control group. Moreover, about a 40% additional decrease in tumor growth was observed, showing a synergistic effect of RDT. SUV_max and TLG showed 47.4±8.8% and 66.5±5.3% decrease at one-week post-treatment, respectively. Also, a higher number of distant metastases were observed using [¹⁸F]FDG PET/CT in the control group than in the RDT group. <h3>Conclusion</h3> Assessment of radiodynamic therapy combined with 5-ALA administration and 15 MV high-energy radiation treatment showed improved treatment outcomes compared to the control, RT only, and 5-ALA only groups. Tumor growth delay and tumor activity suppression were significantly improved. Moreover, a synergistic effect of 5-ALA and 15 MV photon beams was observed. The preliminary (hypothesis-generating) results advocate a further investigation into larger sample sizes.