Ultrasound Modulates Fluorescence Strength and ABCG2 mRNA Response to Aminolevulinic Acid in Glioma Cells.

Background: 5-Aminolevulinic Acid (5-ALA) photodiagnosis (PD) is an effective method to detect residual tumors during glioma surgery. However, fluorescence strength differs in malignant gliomas, and false-negative fluorescence may result in tumor residue. We investigated the effect of ultrasound on the intracellular level of protoporphyrin IX (PpIX) and expression level of ATP-binding cassette transporter 2 (ABCG2), which is thought to act as a membrane efflux pump of PpIX from cytosol.

Methods: The malignant glioma cell lines SNB19, U87MG, and T98G were used for in vitro experiments. Cultured cells underwent ultrasound irradiation (1 MHz, 3 W/cm, duty cycle 10%) after administration of 5-ALA, and morphological changes in tumor cells were observed. PpIX levels and ABCG2 expression were evaluated.

Results: The glioma tumor cells showed transient morphological changes and detachment from the culture dish; however, most cells survived and reverted to their original morphology within 6 hours. PpIX expression levels increased in glioma cells after ultrasound irradiation, and the increase was earlier and greater than that for 5-ALA alone. ABCG2 expressions increased after 5-ALA administration but were lower in ultrasound-irradiated glioma cells.

Conclusions: Ultrasound irradiation of malignant gliomas contributes to stronger 5-ALA-induced fluorescence by elevating intracellular PpIX levels. Suppression of ABCG2 expression by ultrasound may contribute to PpIX accumulation in glioma cells.