title: WR2721 protection of bone marrow in 131I-labeled antibody therapy.
abstract: The use of phosphorothioate radioprotectors such as WR2721 in radioimmunotherapy is attractive because radiation delivered to tumors is usually separated in time from that delivered to the marrow and most normal organs, making protection of tumors of little consequence. However, to be effective radioprotectors must provide continuous protection against radiation of varying dose rates. To evaluate the potential of radioprotectors in radioimmunotherapy we treated normal mice with graded amounts of WR2721 in combination with an LD90/30 (26 MBq) of 131I-labeled antibody. A regimen of 15 doses of WR2721, 200 mg/kg prior to antibody infusion followed by 100 mg/kg ip every 4 h for a total of 72 h, was the maximum tolerated dosage schedule. With this schedule, treatment with radioprotectors failed to prolong survival or delay myelosuppression from the 131I-labeled antibody. In contrast, this regimen of radioprotector provided partial protection from a single treatment of 10 Gy total-body radiation given at 0.2 Gy/min. Protection 30 min after the final dose of WR2721 was greater than 3 h after the 14th dose (60 min prior to the final dose). These results suggest that the potential role of phosphorothioate radioprotectors in a radioimmunotherapy is limited because of the difficulty in achieving continuous protection with nontoxic amounts of drug and possibly because of a limited effect on low-dose-rate radiation.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
authors.forename: C C
authors.initials: CC
authors.lastname: Badger
authors.forename: J
authors.initials: J
authors.lastname: Rasey
authors.forename: C
authors.initials: C
authors.lastname: Nourigat
authors.forename: D R
authors.initials: DR
authors.lastname: Fisher
authors.forename: T E
authors.initials: TE
authors.lastname: Hui
authors.forename: Z M
authors.initials: ZM
authors.lastname: Wu
authors.forename: I D
authors.initials: ID
authors.lastname: Bernstein
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects*; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D007958:Leukocyte Count / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D011829:Radiation Dosage; D013047:Specific Pathogen-Free Organisms; D014916:Whole-Body Irradiation
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D004999:Amifostine