A fundamentally new direction in embolization using reactive chemistry in a swine model

Liver cancer carries a poor prognosis and incidence continues to increase. The main therapy for unresectable disease > 3 cm in diameter is Transarterial Chemoembolization. Unfortunately, overall survival for these patients has improved little in the past two decades. To address this, we propose a new approach using a chemical reaction in situ. We report here our results in a pilot study using a swine model. Domestic swine (n = 3) were treated in the liver with dichloroacetic anhydride in ethiodized oil. CT imaging was followed 24 h after the procedure by necropsy, histopathology, and mass spectrometry imaging. Animals tolerated the procedure well. Imaging showed that the solution remained stable over 24 h. Areas of coagulative necrosis were identified at histopathology. Multiplex immunofluorescence showed focal areas where antibodies did not bind. Similarly, mass spectrometry imaging showed areas of low-abundance or absent molecular ions and new molecular ions in treated areas. The data presented here provide the first direct evidence that reactive embolization results in fundamental changes in tissue architecture down to the molecular level, suggesting significant therapeutic potential. These encouraging results open a wide new field of image-guided in vivo chemistry worthy of further exploration.