title: Fiber-optic system for dual-modality imaging of glucose probes 18F-FDG and 6-NBDG in atherosclerotic plaques.
abstract: 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 18F 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 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.
  
  
  RESULTS
  Our 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 × 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 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.
  
  
  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.
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America; Division of Radiation Physics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Raiyan T
authors.initials: RT
authors.lastname: Zaman
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kosuge
authors.affiliation: Division of Radiation Physics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Guillem
authors.initials: G
authors.lastname: Pratx
authors.affiliation: Division of Radiation Physics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Colin
authors.initials: C
authors.lastname: Carpenter
authors.affiliation: Division of Radiation Physics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Michael V
authors.initials: MV
authors.lastname: McConnell
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging*; D003952:Diagnostic Imaging; D005336:Fiber Optic Technology; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005944:Glucosamine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C045400:6-deoxy-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aminoglucose; D009327:4-Chloro-7-nitrobenzofurazan; D005944:Glucosamine