title: High-resolution optical molecular imaging of changes in choline metabolism in oral neoplasia.
abstract: This study was aimed at developing an optical molecular imaging approach to measure differences in uptake and intracellular retention of choline in clinically isolated tissue biopsies from head and neck cancer patients. An optically detectable analogue of choline (propargyl choline) was synthesized and evaluated in 2D and 3D models and clinically isolated paired biopsies (n = 22 biopsies). Fluorescence contrast between clinically abnormal and normal tissues based on uptake and intracellular retention of propargyl choline was measured and correlated with pathologic diagnosis. Results in 2D and 3D models demonstrated a rapid uptake of propargyl choline in cancer cells, uniform permeation in tissue models, and specific detection of intracellular entrapped propargyl choline using the click chemistry reaction with an azide-modified Alexa 488 dye. Fluorescence imaging measurements following topical delivery of propargyl choline in clinically isolated biopsies showed that the mean fluorescence intensity (MFI) of neoplastic tissues was four-fold to five-fold higher than the MFI of clinically and pathologically normal samples. This difference in fluorescence contrast was measured on the basis of comparison of paired biopsy sets isolated from individual patients as well as comparison of clinically abnormal and normal biopsies independent of anatomic locations in the head and neck cavity and across diverse patients. In conclusion, a novel imaging approach based on monoalkyne-modified choline was developed and validated using cell and tissue models. Results in clinically isolated tissue biopsies demonstrate a significant fluorescent contrast between neoplastic and normal tissues and illustrate high specificity of the optical imaging approach.
authors: Department of Biological and Agricultural Engineering, University of California, Davis, Davis, CA.
authors: Zhen
authors: Z
authors: Luo
authors: Melissa
authors: M
authors: Loja
authors: D Greg
authors: DG
authors: Farwell
authors: Quang C
authors: QC
authors: Luu
authors: Paul J
authors: PJ
authors: Donald
authors: Deborah
authors: D
authors: Amott
authors: Regina
authors: R
authors: Gandour-Edwards
authors: Nitin
authors: N
authors: Nitin