Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent.
Gadolinium(III) texaphyrin (Gd-tex) was recently proposed as a radiosensitizing agent that combines preferential tumor uptake with detection of drug localization by magnetic resonance imaging (S. W. Young et 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 previously reported studies on Gd-tex in HT-29 cells, we tested five other human tumor cell lines (U-87 MG, U251-NCI, SW480, A549, and MCF-7). These studies included a Gd-tex treatment period of 24 h before irradiation (as in the original publication), with concentrations of Gd-tex ranging from 20-500 microM. In neither the HT-29 cells nor any of the other five human cell lines 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 questions about the efficacy of Gd-tex as a radiosensitizing agent.
Bernhard
E J
EJ
University of Pennsylvania, Department of Radiation Oncology, Philadelphia 19104, USA. bernhard@mail.med.upenn.edu
Mitchell
J B
JB
Deen
D
D
Cardell
M
M
Rosenthal
D I
DI
Brown
J M
JM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D019073:HT29 Cells / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D008665:Metalloporphyrins; D011838:Radiation-Sensitizing Agents; C437683:motexafin gadolinium