TY - JOUR
T1 - Evaluation and clinically relevant applications of a fluorescent imaging analog to fluorodeoxyglucose positron emission tomography
AU - Sheth, Rahul A.
AU - Josephson, Lee
AU - Mahmood, Umar
N1 - Funding Information:
The authors wish to express their appreciation to Brett Marinelli for his assistance with the PET/CT imaging, and to Shena Hembrador for her assistance with the FDG cell uptake experiments. This research was supported in part by the Susan G. Komen for the Cure Foundation, as well as NIH grants P50CA127003 and R01-EB001872.
PY - 2009
Y1 - 2009
N2 - A fluorescent analog to 2-deoxy-2 [18F] 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 scizures versus control, and in subcutaneous tumors after the animals are kept nil per os (NPO) for 24 h versus ad libidum 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 FDGPET to extend the applicability of metabolic imaging to minimally invasive and intraoperative settings.
AB - A fluorescent analog to 2-deoxy-2 [18F] 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 scizures versus control, and in subcutaneous tumors after the animals are kept nil per os (NPO) for 24 h versus ad libidum 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 FDGPET to extend the applicability of metabolic imaging to minimally invasive and intraoperative settings.
KW - FDG-PET
KW - Fluorescence biomarkers
KW - Fluorescence endoscopy
KW - Intraoperative imaging
KW - Metabolic imaging
KW - Minimally invasive imaging
KW - Optical molecular imaging
KW - Quantitative imaging
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U2 - 10.1117/1.3259364
DO - 10.1117/1.3259364
M3 - Article
C2 - 20059252
AN - SCOPUS:70449864499
SN - 1083-3668
VL - 14
JO - Journal of biomedical optics
JF - Journal of biomedical optics
IS - 6
M1 - 064014
ER -