Abstract
Purpose: We have developed and tested a novel conjugation of the clinically used prodrug aminolevulinic acid with 2-deoxyglucosamine as a novel probe (ALA-2DG) for fluorescence imaging and photodynamic therapy. Procedures: ALA-2DG was successfully synthesized, and the mechanisms of probe uptake, PpIX synthesis, and photodynamic therapy efficacy were evaluated in vitro and in vivo. Results: ALA-2DG led to PpIX synthesis in tumor cells in vitro and in tumor in vivo. Competitive and inhibitory assays in vitro showed a reduction of this PpIX synthesis that was not observed when cells were incubated with ALA itself, indicating that intracellular uptake of ALA-2DG occurs by GLUT-mediated active transport. Initial photodynamic therapy studies confirmed the efficacy of ALA-2DG as a photodynamic sensitizer. Conclusions: The in vitro assays suggest that ALA-2DG is taken up by cells via glucose transporters. Initial studies in oral cancer demonstrated the applicability of ALA-2DG for in vivo imaging and its potential as an alternative to ALA-PpIX-based fluorescence diagnostics and photodynamic therapy, providing higher tumor specificity.
Original language | English (US) |
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Pages (from-to) | 495-503 |
Number of pages | 9 |
Journal | Molecular Imaging and Biology |
Volume | 16 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2014 |
Keywords
- 2-DG
- 2-Deoxyglucose
- ALA-2DG
- Aminolevulinic acid
- Optical imaging
- Photodynamic therapy
ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
- Cancer Research