Radiodynamic Therapy Using Local Administration of 5-Aminolevulinic Acid for In Vivo Osteosarcoma Xenograft Model

5-Aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PpIX), a radiosensitizer that selectively accumulates in tumor cells. Radiodynamic therapy (RDT) using 5-ALA has demonstrated antitumor effects after systemic administration; however, its efficacy after local administration remains unclear. This study evaluated the therapeutic efficacy of RDT using locally administered 5-ALA in an osteosarcoma xenograft mouse model.

The murine osteosarcoma cell line (LM8) was subcutaneously inoculated into the backs of 5-week-old male BALB/c mice. After tumor establishment (tumor diameter >10 mm), the mice were randomly assigned to three groups (n=5 per group): control (no treatment), irradiation alone (Rx group; single dose of 5 Gy), and 5-ALA RDT group. In the RDT group, 5-ALA (25 mg/kg equivalent; 500 μg/ml, 1 ml) was locally administered to the peritumoral region, followed by a single dose of 5 Gy X-ray irradiation. Tumor volume and body weight were measured over two weeks. The primary outcome was the change in tumor volume.

Fourteen days after treatment, tumor growth was significantly suppressed in the 5-ALA RDT group compared to the control and irradiation groups. No significant differences in body weight were observed among the groups, and no abnormal behaviors were detected. Radiodynamic therapy with locally administered 5-ALA demonstrated significant antitumor effects in a murine model of osteosarcoma. Despite the reduced dose compared to systemic administration, local delivery effectively enhanced the radiosensitizing effect.

The local administration of 5-ALA represents a promising and less toxic therapeutic strategy for osteosarcoma.