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

✍ Scribed by Benjamin L. Viglianti; Sheela A. Abraham; Charles R. Michelich; Pavel S. Yarmolenko; James R. MacFall; Marcel B. Bally; Mark W. Dewhirst

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 885 KB
• Volume: 51
• Category: Article
• ISSN: 0740-3194
• DOI: 10.1002/mrm.20074

✦ Synopsis

Abstract

The purpose of this study was to determine if MnSO~4~/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 MnSO~4~ concentration. Using a temperature‐sensitive liposome formulation, it was found that MnSO~4~ release significantly shortened T~1~. This feature, therefore, suggests that content release can also be measured with these MnSO~4~‐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 (39–40°C). 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. Magn Reson Med 51:1153–1162, 2004. © 2004 Wiley‐Liss, Inc.