In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI: Illustration of targeted delivery

The purpose of this study 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 T-1 shortening correlates with MnSO4 concentration. Using a temperature-sensitive liposome formulation, it was found that MnSO4 release significantly shortened T-1 This feature, therefore, suggests that content release can also 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, nonthermally sensitive liposomes selectively but heterogeneously accumulated in the tumor region. The thermally sensitive liposomes showed a clear pattern of accumulation at the periphery of the tumor, concordant with the release temperature of this formulation (39-40degreesC). 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. (C) 2004 Wiley-Liss, Inc.