Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma

Abstract

Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported methods to markedly increase the specific activity of rhenium-186 ( 186Re)liposomes. To better characterize the potential delivery, toxicity, and efficacy of the highly specific activity of 186Re-liposomes, we evaluated their intracranial application by convection-enhanced delivery in an orthotopic U87 glioma rat model. After establishing an optimal volume of 25 L, we observed focal activity confined to the site of injection over a 96-hour period. Doses of up to 1850 Gy were administered without overt clinical or microscopic evidence of toxicity. Animals treated with 186Re-liposomes had a median survival of 126 days (95 confidence interval [CI], 78.4173 days), compared with 49 days (95 CI, 4453 days) for controls. Log-rank analysis between these 2 groups was highly significant (P= . 0013) and was even higher when 100 Gy was used as a cutoff (P