Chemodosimetry of in-vivo tumor liposome/drug concentration using MRI
The goal of this dissertation project was to determine if MnSO4 /Doxorubicin (DOX) loaded liposomes could be used for in-vivo monitoring of liposome concentration distribution and drug release using MRI. In vitro results show that T1 shortening correlates with MnSO4 concentration. Using a temperature sensitive liposome formulation, it was found that MnSO4 release significantly shortened T1. This feature enables content release to be measured with these MnSO4 loaded liposomes. The feasibility of monitoring this drug delivery and release-imaging agent was shown in a murine tumor model. Upon tumor heating, non-thermally sensitive liposomes selectively but heterogeneously accumulated in the tumor region. The thermally sensitive liposomes showed a clear pattern of enhancement at the periphery of the tumor, concordant with the release temperature of this formulation (39–40°C). The degree of T1 shortening was measured and converted to DOX concentration. This MRI measured concentration was compared to direct histological measurements using fluorescence microscopy of identical regions of interest. There was a linear relationship with a slope and intercept that statistically include 1.0 and 0.0, suggesting that MRI can be used to quantify the distribution DOX delivered in thermal and non-thermally sensitive liposomes.
This liposome contrast agent has potential for use with hyperthermia, by providing individualized monitoring of tissue drug concentration distribution during or after treatment. This would allow for: (1) modification of treatment variables to improve the uniformity of drug delivery and (2) provide a means to select patients most likely to benefit from this liposomal drug treatment. Additionally, the drug loading method used for this liposome is applicable to a wide range of drugs, thereby broadening its applicability. The method is also applicable to other liposomal formulations with triggered release mechanisms.