Potential of using low density lipoproteins (LDLs) as carriers of radioimaging agents for the early identification of atherosclerotic lesions and cervical cancer cells

Xiao, Wu (1999) Potential of using low density lipoproteins (LDLs) as carriers of radioimaging agents for the early identification of atherosclerotic lesions and cervical cancer cells. Masters thesis, Memorial University of Newfoundland.

[English] PDF (Migrated (PDF/A Conversion) from original format: (application/pdf)) - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (13MB) [English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. (Original Version)

Abstract

Atherosclerosis is the underlying factor leading to such cardiovascular diseases (CVD) as stroke, aneurysm, and myocardial infarction. The early detection of atherosclerotic plaques is considered to be crucial for successful prevention and/or therapeutic and dietary intervention of CVD. Current diagnostic practice, on the other hand, can only detect the problem at an advanced stage. The purpose of the work in this thesis was to examine the potential of using non-hydrolyzable radioimaging agents /acetylated low density lipoprotein (AcLDL) conjugates as diagnostic drugs for the early and non-invasive detection of atherosclerosis and for the monitoring of the effects of drug therapy. -- Cholesteryl iopanoate (CI), a cholesteryl ester analog, 1,3-dihydroxypropan-2- one 1,3-diiopanoate (DPIP), a diglyceride analog, and a new compound, cholesteryl 1,3-diiopanoate glyceryl ether (C2I), were synthesized, radiolabeled, and incorporated into AcLDL to use as radiotracers for testing their potential clinical use in the early diagnosis of atherosclerosis in experimental rabbits. Biodistribution of these agents was studied, and aortae of both atherosclerotic lesioned and control rabbits were removed for Sudan IV staining and autoradiography in order to confirm the formation of the atherosclerotic lesion and localization of radioactivity respectively. -- The injected drugs were found to be cleared from blood following a two compartment model. All of the three drugs were shown to be resistant to hydrolysis In vivo. Radioactivity in the atherosclerotic aorta was found to be significantly higher than that in normal aorta in terms of CI and C2I compounds, suggesting that both of the proposed diagnostic probes were selectively taken up by the atherosclerotic lesions. The autoradiography and staining results confirmed that the localization of the proposed probes was superimposed with the atherosclerotic lesion site. Work in this regard was published in part (Xiao et al., 1999a) and summarized in Chapter 2. -- Other work included in this thesis contains a method we developed in our lab to significantly enhance the drug loading efficiency into LDL using a microemulsion with seal oil as the major constituent (see Xiao et al., 1999b and Chapter 3 for details), and the research on the potential of using DPIP loaded LDL as a tumor imaging agent for the detection of cervical tumors (see Xiao et al., 1999c and Chapter 4 for details).

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