Image-guided chemistry altering biology: An in vivo study of thermoembolization

Abstract

Rationale Advances in image-guided drug delivery for liver cancer have shown a significant survival benefit. However, incomplete treatment is common and residual disease is often found in explanted liver specimens. In addition, the need to treat a malignancy from multiple mechanisms at the same time for optimal outcomes is becoming more widely appreciated. To address this, we hypothesized that an exothermic chemical reaction could be performed in situ. Such a strategy could in principle combine several angles of attack, including ischemia, hyperthermia, acidic protein denaturation, and metabolic modulation of the local environment. Methods The University of Texas MD Anderson Cancer Center Institutional Animal Care and Use Committee approved this study. Outbred swine (25–35 kg, 5 control and 5 experimental) were treated under general anesthesia. Embolization was performed with coaxial microcatheter technique in a segmental hepatic arterial branch using either ethiodized oil as control or with thermoembolic solutionBlood samples were obtained before, immediately after, and the day following the procedure just before CT scans and euthanasia. Livers were explanted and samples were obtained for histologic analysis. Results All animals survived the procedure and laboratory values of the control and experimental groups remained within normal limits. The control group had a diffuse or cloudy pattern of attenuation on follow-up CT scan the day after, consistent with gradual antegrade sinusoidal transit of the embolic material. The experimental group had clearly defined vascular casts with some degree of peripheral involvement. At histology, the control group samples had the appearance of normal liver, whereas the experimental group had coagulative necrosis in small pale, punctate areas extending several hundred microns away from the treated vessels and a brisk inflammatory response just outside the margins. Conclusion In situ chemistry via thermoembolization shows early promise as a fundamentally new tactic for image-guided therapy of solid tumors.