Optical glucose analogs of aminolevulinic acid for fluorescence-guided tumor resection and photodynamic therapy.

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. ALA-2DG was successfully synthesized, and the mechanisms of probe uptake, PpIX synthesis, and photodynamic therapy efficacy were evaluated in vitro and in vivo. 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. 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.