REVERSIBLE GELS FOR DELIVERY OF MEDICAL RADIOISOTOPES

Battelle Pacific Northwest Laboratories, Richland WA

Investigators

Abstract

Traditional radiation therapy regimens are designed to deliver 60 to 120 Gy to solid tumors inside the body. The amount delivered is limited by normal tissue tolerance. There is new evidence, however, that very high doses (5,000 to 12,000 Gy) of radiation may be required to destroy many types of solid tumors-especially those that resist conventional treatment. Very high, localized doses deep within the patient can only be achieved with brachytherapy or direct injection of a suitable radionuclide in a suitable delivery vehicle that would assure localization of the radionuclide. To improve the efficacy of injectable brachytherapy we propose a new class of delivery vehicles based on thermoreversible polymeric gels that exhibit fast transition between solution and gel state when heated from ambient to body temperature. The proposed new system will be composed of thermoreversible polymeric gel and a medical radionuclide in a colloidal form. The unique aspect of this novel system is that at body temperature the polymer will undergo a phase transition resulting in entrapment of the radionuclide within the thermally reversible gel matrix and at room temperature the polymer- radionuclide system will be a free flowing, injectable suspension. The injection of polymer/radionuclide suspension into a solid tumor will result in an immediate gel formation causing the localization of therapeutic radiation. The first objective of this research is to synthesize and characterize a family of temperature sensitive polymers and investigate their gel forming properties in the presence of selected medical radionuclides. These polymers will be composed of N- isopropylacrylamide (NiPAAm) and hydrophilic comonomers. The influence of radionuclides on polymer gelation, the effectiveness of radionuclide entrapment and possible polymer radiolysis will be evaluated. The subsequent in vivo studies will involve investigating polymer toxicity, the extent of tissue perfusion by a geling polymer/radionuclide composite, localization of the composite and its efficacy in treating model mouse tumors with alpha and beta emitters.