Abstract/Details

Chemodosimetry of in-vivo tumor liposome/drug concentration using MRI


2004 2004

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Abstract (summary)

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.

Indexing (details)


Subject
Biomedical research;
Radiology;
Oncology
Classification
0541: Biomedical research
0574: Radiology
0992: Oncology
Identifier / keyword
Health and environmental sciences; Applied sciences; Chemodosimetry; Liposomes; Tumor
Title
Chemodosimetry of in-vivo tumor liposome/drug concentration using MRI
Author
Viglianti, Benjamin Logan
Number of pages
203
Publication year
2004
Degree date
2004
School code
0066
Source
DAI-B 65/12, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780496894222, 0496894226
Advisor
Dewhirst, Mark W.
University/institution
Duke University
University location
United States -- North Carolina
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3157014
ProQuest document ID
305179892
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305179892
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