Noninvasive monitoring and evaluation of local drug delivery in livers following radio frequency ablation

The development of local drug delivery therapies has been limited by the lack of appropriate quantitative methods of examining the processes taking place at the target site following implantation of the device. This work focuses on the development of a noninvasive method for studying the in vivo properties of a biodegradable drug delivery system. X-ray computed tomography (CT) is optimized and utilized as a noninvasive technique to characterize the local delivery of platinum-containing anticancer drugs (such as carboplatin) as they are released from the implant in rabbit livers. The effect of tissue structure and composition on the release rate and penetration of agents delivered from model devices is examined, followed by a comparison of in vivo and in vitro release studies. Furthermore, local carboplatin delivery is evaluated in the treatment of liver tumors in a rabbit model. Information acquired from these experiments will be instrumental in the rational design of polymer implants that will be more effective in their clinical application.; On a larger scale, this work represents the initial phase of a research strategy to develop a dual phase, image-guided local therapy for the minimally invasive treatment of liver tumors. In this procedure, tumors will first be thermally ablated using a needle electrode placed directly into the tumor. Subsequently, a controlled-release drug delivery device will be percutaneously placed into the center of the ablated tumor to provide a sustained, elevated concentration of anti-cancer drug that will eliminate surviving cancer cells.; In this work we utilize the computed tomography method to characterize the release and transport of platinum-containing drugs in vivo and evaluate the ablation/millirod therapy scheme. The central hypothesis of this research is that noninvasive monitoring of local drug delivery using CT will lead to a better understanding of the drug pharmacokinetics in vivo for device optimization that cannot be normally observed with in vitro or ex-vivo analysis.