Feasibility study using tissue as reagent for cancer therapy: endovascular ablation via thermochemistry

Abstract

The growing global burden of hepatocellular carcinoma, the poor response to chemotherapies such as sorafenib, and the inoperable status of most patients when they present clinically have led, over the last 3 decades, to development and application of loco-regional therapies such as ablation and embolization. Unfortunately, incomplete treatment and local recurrence are all too common with these methods. In this report, we describe a fundamentally new strategy, an image-guided embolization method employing a targeted chemical reaction to affect local biology. We demonstrate feasibility in a simple model system using an acid chloride as the electrophile in an inert carrier solvent. The reagent solution is delivered through a small catheter in the target artery. Once released, the acid chloride reacts vigorously with any water or available functional groups present such as hydroxyl or amino groups in the tissue and simultaneously generates an acidic local environment. We call this new method thermoembolization due to the exotherm that is observed in the tissues as captured by both thermocouple and infrared measurements. The in-situ reaction of a small volume of the electrophile delivered intra-arterially causes highly localized endovascular ablation in our model system. The ratio of coagulated tissue volume to injected material was consistently in the range of 40:1 which compares very favorably against the 1:1 ratio found in chemical ablation using direct, intratumoral ethanol injection. The largest increase in temperature observed was 24.1°C, meaning that the thermal energy alone could be enough to coagulate tissues. The acid that is released at the same locale further enhances the denaturation observed. Taken together, these findings underscore the potential of this new approach for treating malignancies in a nonsurgical way.