Fiber-Optic System for Dual-Modality Imaging of Glucose Probes (18)F-FDG and 6-NBDG in Atherosclerotic Plaques

BACKGROUND: Atherosclerosis 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 (18)F and fluorescent glucose probes, and (2) validating the system on ex vivo murine plaques. METHODS: A novel design implements a flexible fiber-optic catheter consisting of both a radio-luminescence and a fluorescence imaging system to detect radionuclide (18)F-fluorodeoxyglucose ((18)F-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 (18)F-FDG or 6-NBDG. Confirmatory optical imaging by IVIS-200 and autoradiography were also performed. RESULTS: Our fiber-optic imaging system successfully visualized both (18)F-FDG and 6-NBDG probes in atherosclerotic plaques. For (18)F-FDG, the ligated left carotid arteries (LCs) exhibited 4.9-fold higher radioluminescence signal intensity compared to the non-ligated right carotid arteries (RCs) (2.6×10(4)±1.4×10(3) vs. 5.4×10(3)±1.3×10(3) A.U., P = 0.008). Similarly, for 6-NBDG, the ligated LCs emitted 4.3-fold brighter fluorescent signals than the control RCs (1.6×10(2)±2.7×10(1) vs. 3.8×10(1)±5.9 A.U., P = 0.002). The higher uptake of both (18)F-FDG and 6-NBDG in ligated LCs were confirmed with the IVIS-200 system. Autoradiography further verified the higher uptake of (18)F-FDG by the LCs. CONCLUSIONS: This 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.