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

Fumio Yamaguchi, Takayuki Asakura, Hiroshi Takahashi, Takayuki Kitamura, Akira Teramoto

Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.

DOI: 10.4236/jct.2013.41025                

Abstract

We investigated the feasibility of sonodynamic therapy for glioma by low frequency ultrasoundwith5-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.

Keywords

Glioma; Sonodynamic Therapy; 5-Aminolevulinic Acid; Protoporphyrin IX; Ultrasonication

Conflicts of Interest

The authors declare no conflicts of interest.

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