Iodinated Cyanoacrylate-Based Novel Liquid Embolic Compositions with Inherent Radiopacity for Endovascular Embolization.

Abstract

Endovascular embolization is a promising therapeutic approach broadening its application area due to its minimal invasiveness and short operation time, wherein lesional blood vessels are occluded with liquid embolic agents under X-ray imaging guidance. Histoacryl and its composition with Lipiodol are one of the most widely used liquid embolic agents, however, Histoacryl has critical limitations, such as lack of innate X-ray visibility and strong adhesion to microcatheter. In this study, three different iodinated cyanoacrylates are newly synthesized as alternatives to Histoacryl and employed to develop liquid embolic compositions. Among them, 4-iodobutyl 2-cyanoacrylate (IBCA) is most preferable with high iodine content (730 mgI mL^-1) and fast polymerization. The IBCA-based embolic compositions containing ethyl oleate and acetic acid showed moderate viscosity and reduced catheter adhesiveness (≈0.80 N), and their polymerization time is freely controllable from 2 to 15 s. In the embolization test with rabbit models, the renal artery is successfully occluded by IBCA-based embolic compositions without vascular recanalization or nontarget embolization for 4 w. Their embolic effect is further evaluated using swine models, demonstrating the practical applicability in the clinic. In conclusion, IBCA and its compositions are determined to have great potential as novel liquid embolic agents.