Enhancement of meta-tetrahydroxyphenylchlorin-sensitized photodynamic treatment on human tumor xenografts using a water-soluble vitamin E analogue, Trolox

Photodynamic therapy (PDT) using meta-tetrahydroxyphenylchlorin (mTHPC) per formed on HT29 human colon adenocarcinoma xenografts in nude mice was shown to be enhanced by Trolox, a water-soluble vitamin E analogue. Trolox, inje cted i.p. at 250 mg/kg body weight 90 min before PDT, delayed tumor doublin g time from 13 (PDT only) to 19 days. Enhancement of the tumoricidal effect of PDT by Trolox required the presence of the drug at the photochemical st age since its injection after irradiation is ineffective. HPLC measurements indicated that I hr after injection the Trolox concentration in plasma was as high as 0.8 mM. In vivo measurements of mTHPC fluorescence in mice trea ted by PDT with or without Trolox injection showed that Trolox did not prot ect mTHPC from photodegradation. Laser flash photolysis studies performed i n solution demonstrated that Trolox reduces triplet mTHPC efficiently (reac tion rate constant 2 x 10(7) M-1.sec(-1)) leading to the formation of radic al products. Kinetic considerations suggest that the Trolox-mediated radica l pathway can work in relay with singlet oxygen in hypoxic conditions, prov iding a possible explanation for the observed enhancement of mTHPC-sensitiz ed PDT by Trolox. (C) 2000 Wiley-Liss, Inc.