Hepatocellular carcinoma (HCC) is an intractable
cancer with a high mortality rate. Transarterial chemoembolization (TACE), a non-curative method, is the first line
therapy for intermediate stage patients. This effectively extends patient survival but requires a complicated intraarterial catheterization procedure and is poorly suited to repeated administration. Here, we investigate gas chemoembolization, a less invasive, more easily administered transient occlusion method that circumvents these limitations. We examined the efficacy of repeated embolization combined with systemically administered
doxorubicin, the most common chemotherapeutic in TACE, or
tirapazamine, a
hypoxia-activated
cytotoxic agent, in an ectopic xenograft model of HCC. Emboli were generated in situ using acoustic droplet vaporization, the noninvasive focused ultrasound-mediated conversion of intravenously administered
perfluorocarbon microdroplets into
microbubbles. Gas embolization alone significantly reduced the Ki67 index and
tumor viability (11.6 ± 6.71% non-necrotic vs 100% in control; p < 0.01) after 3 treatments, as assessed by histological analysis. Mice treated for three weeks exhibited significant
tumor regression compared to control (23.8 ± 5.37% of initial volume vs 427 ± 49.7% in controls, p < 0.01), irrespective of the chosen chemotherapeutic agent. However, an additional three weeks of monitoring post-treatment elucidated a significant difference in the
tumor recurrence rate, with combined gas embolization and
doxorubicin resulting in the best treatment outcomes (60% complete regression). While
doxorubicin administration resulted in significant
cardiotoxicity (p < 0.01), it strongly interacted with the droplet shells, reducing the systemic dose by 11.4%. Overall, gas chemoembolization shows promise as a developmental
therapy and merits further study in more complex
tumor models.