Sonodynamic treatment of murine tumor through second-harmonic superimposition

Acoustic cavitation is the primary mechanism of sonochemical reaction and has potential use for tumor treatment in combination with a certain sonodynamically active agent. It has been known that inducing cavitation with progressive waves is more difficult than with standing waves. This may have been limiting the sonodynamic treatment of tumors. We found that ultrasonically induced chemical reactions are greatly accelerated when the second harmonic is superimposed onto the fundamental. Experimental murine tumors were treated with progressive waves in combination with administration of a gallium-porphyrin complex (ATX-70). The tumors treated with second-harmonic superimposition stopped growing for about 2 days and then gradually started growing again. When only 0.5 MHz was used, tumor growth was not significantly different from that in untreated tumors. It was significantly slower than the untreated when only 1.0 MHz was used, but it was significantly further slowed when second-harmonic superimposition was used. The tumor-bearing mice treated with second-harmonic superimposition after ATX-70 administration survived 5 days longer on average than those untreated.