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.
Highlights
Glioma has an invasive nature and often invades into the proximity of critically functioning structures
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
Antitumor Effect Sonodynamic therapy is an approach based on the synergistic effect of ultrasound and chemical compound referred to as “sonosensitizer” for cancer treatment
Summary
Glioma has an invasive nature and often invades into the proximity of critically functioning structures. Even though it is a standard therapy, often results in postoperative neurological deteriorations To avoid this sequel, photodynamic therapy is a promising technique to kill tumor tissue selectively near the functioning brain tissue. In this study we investigated the feasibility of sonodynamic therapy with relatively low frequency ultrasound of 25kHz which is often used in ultrasonic surgical aspirators [9,10]. This is a first report on the utilization of low-frequency ultrasound for sonodynamic therapy of human glioma. 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
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