Pharmaceutical Sciences ETDs

Publication Date

8-25-2016

Abstract

The objective of this thesis project is to assess inflammatory leukocyte presence and accumulation in vascular atherosclerotic plaque using [111In] In-DANBIRT as a non-invasive diagnostic imaging tool. ApoE-/-mice were fed either normal or high fat diet (HFD) for 8 weeks. Sprague Dawley male rats were exposed to filtered air and ozone for 4 hours. SPECT/CT imaging was performed at baseline, 4 and 8 weeks. 3D autoradiography was performed after 8 weeks. Leukocyte isolation methods were performed for neutrophil and peripheral blood mononuclear cell (PBMC) separations post-incubation with [68Ga] Ga-DANBIRT and [111In] In-DANBIRT. Whole blood isolation correlated these findings showing increased specific uptake by neutrophils in the ozone-exposed group. Radioisotopic dilution methods evidence a saturation of binding sites in isolated neutrophil samples starting at a 10-fold dilution from initial concentration of [111In] In-DANBIRT. Longitudinal molecular imaging evidenced an increased uptake in HFD fed mice, consistent with increased immune response to vascular injury in cardiovascular and immune tissues. Histologic analysis illustrated atherosclerotic plaque disease progression and increased vascular lesion area in HFD fed mice.

First Committee Member (Chair)

Norenberg, Jeffrey

Degree Name

Pharmaceutical Sciences

Second Committee Member

Campen, Matthew

Level of Degree

Masters

Third Committee Member

Garver, William

Department Name

College of Pharmacy

Project Sponsors

Keck-UNM Small-Animal Imaging Resource Shared Resource Center University of New Mexico Health Sciences Center University of New Mexico Comprehensive Cancer Center University of New Mexico College of Pharmacy Anesthesiology Pain Research Laboratory National Institutes of Health

Language

English

Document Type

Thesis

Keywords

Atherosclerotic, inflammatory, vascular, Leukocyte Function Associated Antigen-1 (LFA-1), [111In] In-DANBIRT, neutrophils, High Fat Diet (HFD)

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