Abstract 5553: Liposomal rhenium by convection enhanced delivery for primary brain tumors

Abstract

Abstract Introduction: While adjuvant external beam radiation prolongs survival in glioblastoma, doses must be limited to approximately 60Gy secondary to lack of benefit and increased toxicity with higher doses. Despite maximum radiation, 90% of tumors recur at the original site. Convection enhanced delivery (CED) of radiation has the potential of administering higher doses locally to the tumor while reducing toxicity to normal brain parenchyma. Lipid nanocarriers offer the potential of distribution though the tumor as well as retention within the tumor. We hypothesized that a radionuclide liposome generated with a specially developed chemistry for loading a large quantity of rhenium, delivered by CED, would allow a higher dose of radiation to be delivered safely and effectively. Methods: Intracranial xenografts were established in nude rats with luciferase expressing U87 glioma cell line. To establish the correct volume of administration, liposomes were labeled with technetium99 and administered intratumorally by CED in volumes of 50 and 100ul at variable rates and imaged by SPECT/CT. Once volume and rate were established, an initial dose range finding study was performed with Re186 doses from 25 to 125uCi. The maximum tolerated dose was then assessed for efficacy as well as to confirm absence of toxicity. Tumor growth was followed by in vivo bioluminescent imaging and 7T MRI. Rats were sacrificed when moribund or when marked neurologic deficit was observed. Rat brains were evaluated by standard histologic methods for residual tumor, gliosis and necrosis. Results: Technetium liposomes in smaller volumes appeared to have better local retention with up to 60% retained at 22 hours post injection. Rats bearing U87 tumors treated with liposomal Rhenium186 tolerated the maximum administered dose of 125uCi (∼550Gy) without apparent toxicity, evidence of necrosis or gliosis. Efficacy was confirmed with rats treated at maximum dose, with all rats in the maximum dose continuing to survive and gain weight to 70 days post tumor inoculation, as compared to control rats which expired between 38 and 44 days. Conclusions: High doses (approx 550Gy) can be delivered to intracranial tumors in tumor bearing rats by CED of rhenium nanoliposomes. No evidence of neurotoxicity or histological changes suggestive of normal tissue injury are observed despite these very high doses. Rhenium liposomes delivered by CED show significant antiglioma activity with prolonged survival of treated tumor bearing rats. Further experiments are warranted to evaluate the potential of Rhenium 186 liposome in the treatment of glioblastoma and other primary brain tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5553.