title: In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI: illustration of targeted delivery.
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 degrees 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.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27705, USA.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Viglianti
authors.forename: Sheela A
authors.initials: SA
authors.lastname: Abraham
authors.forename: Charles R
authors.initials: CR
authors.lastname: Michelich
authors.forename: Pavel S
authors.initials: PS
authors.lastname: Yarmolenko
authors.forename: James R
authors.initials: JR
authors.lastname: MacFall
authors.forename: Marcel B
authors.initials: MB
authors.lastname: Bally
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000493:pharmacokinetics*; D005354:Fibrosarcoma / Q000378:metabolism*; D006979:Hyperthermia, Induced; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008081:Liposomes / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D017895:Manganese Compounds / Q000493:pharmacokinetics*; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D013431:Sulfates / Q000493:pharmacokinetics*; D013696:Temperature
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D017895:Manganese Compounds; D013431:Sulfates; D004317:Doxorubicin; C039798:manganese sulfate