Small Molecule Therapeutics Antitumor Effects in Gastrointestinal Stromal Tumors Using Photodynamic Therapy with a Novel Glucose-Conjugated

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Except for surgical resection, no effective treatment strategies have been established. Photodynamic therapy (PDT) consists of intravenous administration of a photosensitizer, activatedby a specificwavelength of light, which produces reactive oxygen species that directly kill tumor cells. We analyzed the efficacy of PDT using a newly developed photosensitizer, 5,10,15,20-tetrakis [4-[b-D-glucopyranosylthio-2,3,5,6-tetra-fluorophenyl]-2,3,[methano[N-methyl] iminomethano] chlorin (H2TFPC-SGlc), for theGIST treatment.Various photosensitizers were administered in vitro to GIST (GIST-T1) and fibroblast (WI-38) cells, followed by irradiation, after which cell death was compared. We additionally established xenograft mouse models with GIST-T1 tumors and examined the accumulation and antitumor effects of thesephotosensitizers in vivo. In vitro, theexpressionof theglucose transportersGLUT1,GLUT3,andGLUT4, thecellularuptakeofH2TFPC-SGlc, and apoptosismediated byPDTwithH2TFPC-SGlcwere significantly higher inGIST-T1 than inWI-38 cells. In vivo, H2TFPC-SGlc accumulationwas higher in xenograft tumors of GIST-T1 cells than in the adjacent normal tissue, and tumor growth was significantly suppressed following PDT. PDT with novel H2TFPC-SGlc is potentially useful for clinical applications about the treatment of GIST. Mol Cancer Ther; 13(4); 767–75. 2014 AACR