Low Frequency Ultrasonication Induced Antitumor Effect in 5-Aminolevulinic Acid Treated Malignant Glioma

We investigated the feasibility of sonodynamic therapy for glioma by low frequency ultrasound with 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX) in heme synthetic process. In vivo tumor model was made by inoculating human glioma cell line U87-MG subcutaneously in nude mice. The tumor was sonicated by 25-kHz ultrasound 4 hours following administration of 5-ALA. The tumor size decreased in 5-ALA administered (ALA(+)US(+)) mice, while increased in non-5-ALA administrated (ALA(−)US(+)) mice and non-sonicated mice (ALA(+)US(−)). The immunohistochemical analysis revealed an apoptotic change in tumor tissue of ALA(+)US(+) mice. The results showed the therapeutic effect of 25 kHz ultrasound for the glioma in 5-ALA administered tumor-bearing mice by inducing apoptotic change of tumor cells. This is a first report to elucidate the feasibility of therapeutic use of 25 kHz, relatively low frequency, ultrasound in sonodynamic therapy using 5-ALA as a sonosensitizer precursor. The utilization of this frequency will contribute to the development of sonodynamic therapy for gliomas and the spread of this technique in many hospitals that possess ultrasonic aspirators.