This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We have shown in animal studies that hyperthermia can be combined with low temperature sensitive liposomes (LTSL) to increase drug delivery to tumors. The LTSL is a specialized liposome formulation that releases its contents (doxorubicin and manganese) at mildly elevated temperatures (42 C), allowing a total tumor drug delivery of 30 times more than free drug. Using MRI, we are able to visualize the liposomes during and after administration (due to manganese used for liposome loading). Our group has recently shown that T1 shortening is linearly correlated to drug concentration (Ben Viglianti and Mark Dewhirst, with CIVM). We hypothesize that a major barrier for drug delivery to tumors is macroscopic variation in drug delivery. Using MR as a tool, we will evaluate drug concentration and distribution with different methods of liposome and hyperthermia therapy. In addition, we propose to correlate drug distribution with tumor response. This may provide a non-invasive way to evaluate drug delivery and predict tumor response in the clinical setting. The MR studies are integral to the above goals. The non-invasive imaging will allow evaluation of drug delivery in vivo with subsequent correlation to tumor response
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