Abstract
BackgroundAtherosclerosis is a progressive inflammatory condition that underlies coronary artery disease (CAD)–the leading cause of death in the United States. Thus, the ultimate goal of this research is to advance our understanding of human CAD by improving the characterization of metabolically active vulnerable plaques within the coronary arteries using a novel catheter-based imaging system. The aims of this study include (1) developing a novel fiber-optic imaging system with a scintillator to detect both 18F and fluorescent glucose probes, and (2) validating the system on ex vivo murine plaques.MethodsA novel design implements a flexible fiber-optic catheter consisting of both a radio-luminescence and a fluorescence imaging system to detect radionuclide 18F-fluorodeoxyglucose (18F-FDG) and the fluorescent analog 6-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-6-Deoxyglucose (6-NBDG), respectively. Murine macrophage-rich atherosclerotic carotid plaques were imaged ex vivo after intravenous delivery of 18F-FDG or 6-NBDG. Confirmatory optical imaging by IVIS-200 and autoradiography were also performed.ResultsOur fiber-optic imaging system successfully visualized both 18F-FDG and 6-NBDG probes in atherosclerotic plaques. For 18F-FDG, the ligated left carotid arteries (LCs) exhibited 4.9-fold higher radioluminescence signal intensity compared to the non-ligated right carotid arteries (RCs) (2.6×104±1.4×103 vs. 5.4×103±1.3×103 A.U., P = 0.008). Similarly, for 6-NBDG, the ligated LCs emitted 4.3-fold brighter fluorescent signals than the control RCs (1.6×102±2.7×101 vs. 3.8×101±5.9 A.U., P = 0.002). The higher uptake of both 18F-FDG and 6-NBDG in ligated LCs were confirmed with the IVIS-200 system. Autoradiography further verified the higher uptake of 18F-FDG by the LCs.ConclusionsThis novel fiber-optic imaging system was sensitive to both radionuclide and fluorescent glucose probes taken up by murine atherosclerotic plaques. In addition, 6-NBDG is a promising novel fluorescent probe for detecting macrophage-rich atherosclerotic plaques.
Highlights
According to the World Health Organization, approximately one third of all deaths in developed countries are related to coronary artery disease (CAD), characterized by the buildup and disruption of atherosclerotic plaques within the coronary wall [1]
This fluorescent probe has been shown to be transported into the cell by the same glucose transporters (GLUT) as glucose, but does not undergo phosphorylation by hexokinase due to the NBD fluorochrome and never enters the glycolytic pathway, a reaction that causes 6-NBDG to accumulate within the cell [18,21]
System detected a 4.9-fold higher radioluminescence signal emission from the ligated left carotid arteries (LCs) post-18F-FDG compared to the control right carotid arteries (RCs) (2.6610461.46103 vs. 5.4610361.36103 A.U., P = 0.008; Figure 3g), with high 18F-FDG signal detected in the heart
Summary
According to the World Health Organization, approximately one third of all deaths in developed countries are related to coronary artery disease (CAD), characterized by the buildup and disruption of atherosclerotic plaques within the coronary wall [1]. Examples include positron emission tomography (PET) with 18F-FDG [5], magnetic resonance imaging (MRI) using ultra-small super-paramagnetic iron oxide (USPIO) probes [6,7], single photon emission computed tomography (SPECT) using VCAM-1-specific 99mTc-labeled peptidic sequences [8], and the iodinated nanoparticulate contrast agent N1177 for computed tomography (CT) [9] Application of these external imaging approaches to coronary atherosclerosis has been challenging due to small coronary size, cardiac motion, and detecting adequate signal and contrast. Atherosclerosis is a progressive inflammatory condition that underlies coronary artery disease (CAD)–the leading cause of death in the United States. The aims of this study include (1) developing a novel fiber-optic imaging system with a scintillator to detect both 18F and fluorescent glucose probes, and (2) validating the system on ex vivo murine plaques
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