1Department of Cancer Survey and Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 2Research & Development Group, Hitachi, Ltd., 3Department of Cancer Prevention, Osaka Center for Cancer and Cardiovascular Diseases Prevention
HIFU, drug delivery system, superheated perfluorocarbon droplet, histotripsy, mechanical effect, cancer
Purpose: The aim of this study was to investigate the combination effects of pulsed HIFU (pHIFU) and phasechange nanodroplets (PCND) as a sensitizer on efficient induction of mechanical effects of pHIFU and chemically enhanced tumor growth inhibition for local anti-tumor therapy. Method: Changes in growth of colon 26 tumor tissue inoculated onto CDF1 mice were evaluated by the following treatments. (1) pHIFU exposure (1.1 MHz, 3.2 kW/cm2, 300 cycles, and 50 ms interval) for 60 s, (2) PCND (1%) injection, (3) adriamycin (4 mg/kg) injection, (4) pHIFU exposure after PCND injection, and (5) pHIFU exposure after PCND+adriamycin injection simultaneously. Results: Significant changes in tumor growth were observed in the group with combination of pHIFU and PCND, although single therapy did not show any significant difference. PCND enhanced mechanical tissue fractionation by pHIFU, which was detectable by Realtime tissue elastography. Moreover, the combination of pHIFU and PCND+Adriamycin suppressed the tumor growth for 2 weeks, and 3 of 4 mice did not show any sign of regrowth during the 30-day observation. Conclusion: The combination of pHIFU and PCND exerted a significant anti-tumor effect and may be a new candidate for treatment of locally advanced cancer.