Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent

Gadolinium(III) texaphyrin (Gd-tex) was recently proposed as a radiosensiti zing agent that combines preferential tumor uptake with detection of drug l ocalization by magnetic resonance imaging (S. W, Young el al,, Proc, Natl, Acad, Sci, USA, 93: 6610-6615, 1996), In view of the initial report on this compound, four radiobiology laboratories undertook independent efforts to further study radiosensitization by Gd-tex, In addition to repeating the pr eviously reported studies on Gd-tex in HT-29 cells, we tested five other hu man tumor cell lines (U-87 MG, U251-NCI, SW480, A549, and MCF-7), These stu dies included a Gd tex treatment period of 24 h before irradiation (as in t he original publication), with concentrations of Gd-tex ranging from 20-500 mu M. In neither the HT-29 cells nor any of the other five human cell line s did we see radiation sensitization by Gd-tex, Two cell lines (MCF-7 and U -87 MG) were further tested for radiosensitization by Gd-tex under hypoxic conditions. No radiosensitization was observed in either case. Finally, the radiation response of two tumor lines were assessed in vivo. Neither HT-29 xenografts in severe combined immunodeficient (SCID) mice nor RIF-1 tumors growing in C3H mice demonstrated radiosensitization after Gd-tex treatment before single or fractionated doses of radiation. Our results raise questi ons about the efficacy of Gd-tex as a radiosensitizing agent.