Lithotripter Shockwave-Induced Enhancement of Mouse Melanoma Lung Metastasis: Dependence on Cavitation Nucleation

Abstract

Purpose: To confirm a previous report of metastasis enhancement by lithotripter shockwaves (LSW) and to test the hypothesis that this effect is attributable to cavitation. Materials and Methods: The metastatic B16-D5 melanoma cell line was implanted on the hind legs of female C57/b16 mice 12 days before tumor treatment. The tumors were treated with 500 LSW in a waterbath arrangement. The effect of augmented cavitation nucleation was tested by intratumor injection of air bubbles or ultrasound contrast agent gas bodies (UCAGB). The primary tumor was surgically removed on day 1 after treatment. The six groups of mice were sham, LSW, sham + air bubbles, LSW + air bubbles, sham + UCAGB, and LSW + UCAGB. Data were collected for the 113 mice that survived at least 25 days. Lung evaluations were performed blind after 2 weeks of bleaching in Fekete's solution. Results: The outcomes of the three sham groups were very similar and indicated that the simple injection of material into the tumor did not increase metastasis. In comparison with the pooled shams, both the LSW + air bubbles and LSW + UCAGB groups had statistically significant increases in metastasis counts. Only the LSW + UCAGB group had a significant increase in incidence of metastasis relative to the pooled shams. The LSW + UCAGB also had significantly reduced survival. Conclusion: Shockwaves can enhance metastasis from tumors, and this effect is attributable to cavitation.