title: Widefield optical imaging of changes in uptake of glucose and tissue extracellular pH in head and neck cancer.
abstract: The overall objective of this study was to develop an optical imaging approach to simultaneously measure altered cell metabolism and changes in tissue extracellular pH with the progression of cancer using clinically isolated biopsies. In this study, 19 pairs of clinically normal and abnormal biopsies were obtained from consenting patients with head and neck cancer at University of California, Davis Medical Center. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) and Alexa 647-pHLIP [pH (low) insertion peptide] was measured noninvasively by widefield imaging, and correlated with pathologic diagnosis. The results of widefield imaging of clinical biopsies demonstrated that 2-NBDG and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. The results also demonstrated the potential of this approach to detect subepithelial lesions. Topical application of the contrast agents generated a significant increase in fluorescence contrast (3- to 4-fold) in the cancer biopsies as compared with the normal biopsies, irrespective of the patient and location of the biopsy within a head and neck cavity. This unpaired comparison across all the patients with cancer in this study highlights the specificity of the imaging approach. Furthermore, the results of this study indicated that changes in intracellular glucose metabolism and cancer acidosis are initiated in the early stages of cancer, and these changes are correlated with the progression of the disease. In conclusion, this novel optical molecular imaging approach to measure multiple biomarkers in cancer has a significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.
authors.affiliation: Department of Biological and Agricultural Engineering, University of California, Davis, Davis, California.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Surgery, Division of Vascular Surgery, University of California, Davis, Davis, California.
authors.forename: Melissa N
authors.initials: MN
authors.lastname: Loja
authors.affiliation: Department of Otolaryngology, University of California, Davis, Davis, California.
authors.forename: D Greg
authors.initials: DG
authors.lastname: Farwell
authors.affiliation: Department of Otolaryngology, University of California, Davis, Davis, California.
authors.forename: Quang C
authors.initials: QC
authors.lastname: Luu
authors.affiliation: Department of Otolaryngology, University of California, Davis, Davis, California.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Donald
authors.affiliation: Department of Otolaryngology, University of California, Davis, Davis, California.
authors.forename: Deborah
authors.initials: D
authors.lastname: Amott
authors.affiliation: Department of Otolaryngology, University of California, Davis, Davis, California.
authors.forename: Anh Q
authors.initials: AQ
authors.lastname: Truong
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, Davis, California.
authors.forename: Regina
authors.initials: R
authors.lastname: Gandour-Edwards
authors.affiliation: Department of Biological and Agricultural Engineering, University of California, Davis, Davis, California. Department of Food Science and Technology, University of California, Davis, Davis, California. nnitin@ucdavis.edu.
authors.forename: Nitin
authors.initials: N
authors.lastname: Nitin
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives; D000138:Acidosis / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D002232:Carbocyanines; D003287:Contrast Media / Q000493:pharmacokinetics; D003847:Deoxyglucose / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000473:pathology; D061848:Optical Imaging; D055095:Optics and Photonics; D011379:Prognosis
chemical_list: C569686:Alexa Fluor 647; D014408:Biomarkers, Tumor; D002232:Carbocyanines; D003287:Contrast Media; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; D005947:Glucose; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose