In Situ β-Irradiation of a Brain Arteriovenous Malformation Model

Abstract

Background and Purpose-The treatment of large brain arteriovenous malformations (BAVMs) is challenging, and embolization alone is seldom curative. The study goal is to enhance the efficacy of arteriovenous malformation embolization by adding a ␤-emitting isotope to the embolic agent. Methods-The pig rete mirabile was used as a BAVM model. The body distribution of radioactivity was evaluated after selective rete injection of N-butyl,2-cyanoacrylate mixed with 131 I-lipiodol in 8 animals using immediate whole body ␥-scintigraphy. Activities within the whole rete mirabile and selected tissue samples were quantified with a gamma counter immediately after sacrifice. Two pigs were submitted to serial ␥-scintigraphies for 6 weeks to detect delayed isotope leaching. Long-term effects of in situ irradiation were evaluated using a mixture of 188 Re/N-butyl,2-cyanoacrylate in 8 pigs. In 1 animal, autoradiography was performed to evaluate local rete mirabile distribution of the radioactivity. Seven pigs were injected with 188 Re/glue in 1 rete mirabile and with glue only on the opposite side, and the degree of vascular occlusion of both sides was compared on histology at 2 (nϭ2) or 6 months (nϭ5).Results-There was negligible activity outside the target. Radiation caused occlusion of vessels unreached by the glue itself but in the vicinity of the radioactive source in 5 of 7 rete mirabile. Conclusions-Selective

Formulation and characterization of radio‐opaque conjugated in situ gelling materials

“…11 The practice of using in situ forming gels to treat AVMs has led to several new models to study their efficacy including in vitro flow models 12 and in vivo animal models using pig rete mirabile. 2,13 A subset of chemically forming in situ gels includes monomers, which polymerize through Michael-Type Addition reaction mechanisms. Michael-Type Addition is observed when nucleophiles, including thiols, conjugate electron withdrawn alkenes, as present in acrylates, in mild basic conditions.…”