title: Evaluation and clinically relevant applications of a fluorescent imaging analog to fluorodeoxyglucose positron emission tomography.
abstract: A fluorescent analog to 2-deoxy-2 [(18)F] fluoro-D-glucose position emission tomography (FDG-PET) would allow for the introduction of metabolic imaging into intraoperative and minimally invasive settings. We present through in vitro and in vivo experimentation an evaluation of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), a fluorescently labeled glucose molecule, as a molecular beacon of glucose utilization. The competitive inhibition of 2-NBDG uptake by excess free glucose is directly compared against FDG uptake inhibition in cultured cells. 2-NBDG uptake in the brain of a mouse experiencing a generalized seizure is measured, as well as in subcutaneously implanted tumors in mice during fed and fasting states. Localization of 2-NBDG into malignant tissues is studied by laser scanning microscopy. The clinical relevance of 2-NBDG imaging is examined by performing fluorescence colonoscopy, and by correlating preoperative FDG-PET with intraoperative fluorescence imaging. 2-NBDG exhibits a similar uptake inhibition to FDG by excess glucose in the growth media. Uptake is significantly increased in the brain of an animal experiencing seizures versus control, and in subcutaneous tumors after the animals are kept nil per os (NPO) for 24 h versus ad libitum feeding. The clinical utility of 2-NBDG is confirmed by the demonstration of very high target-to-background ratios in minimally invasive and intraoperative imaging of malignant lesions. We present an optical analog of FDG-PET to extend the applicability of metabolic imaging to minimally invasive and intraoperative settings.
authors.affiliation: Massachusetts General Hospital, Department of Radiology, Division of Nuclear Medicine and Molecular Imaging, 55 Fruit Street, White 427, Boston, Massachusetts 02114, USA.
authors.forename: Rahul A
authors.initials: RA
authors.lastname: Sheth
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
authors.forename: Umar
authors.initials: U
authors.lastname: Mahmood
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007202:Indicators and Reagents / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography / Q000379:methods; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D012640:Seizures / Q000378:metabolism; D013050:Spectrometry, Fluorescence / Q000379:methods*
chemical_list: D007202:Indicators and Reagents; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; D005947:Glucose; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose