title: Murine hematopoietic ablation by alpha-particle-emitting radiopharmaceuticals - a potential preparative regimen for bone-marrow transplantation.
abstract: Although short-lived alpha-particle-emitting radiopharmaceuticals are currently under evaluation for biologically targeted radiotherapy, very little is known about the dose-response kinetics of the hematosuppression produced by low level or transient exposure to these compounds while in the circulation. We have used hematopoietic progenitor cell colony-forming-unit assays to establish the dose-response curve for Bi-212 alpha particle radiation delivered in vitro, and have compared it to the dose-response curves for equivalent doses of Y-90 beta and Cs-137 gamma radiation. We then evaluated the dose-response effects for these radiopharmaceuticals after in vivo injection in mice. Both in vitro and in vivo, the Bi-212 was extremely hematosuppressive (50% inhibitory dose 20-30 cGy in culture) but this myelosuppression was transient at low or intermediate doses. Serum froin mice recovering from Bi-212-induced hematosuppression produced significant stimulation of naive syngeneic marrow progenitor cells, supporting the existence of a physiologic feedback mechanism that involves a poorly defined humoral factor released after radiation injury. Short-lived alpha emitters may be well suited to the development of tumor-seeking radiopharmaceuticals that can be used in the preparation of patients for autologous and allogeneic marrow transplantation.
authors.affiliation: ARGONNE NATL LAB,DIV BIOL,ARGONNE,IL 60439. ARGONNE NATL LAB,DIV CHEM,ARGONNE,IL 60439.
authors.forename: R
authors.initials: R
authors.lastname: Macklis
authors.forename: B
authors.initials: B
authors.lastname: Beresford
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: R
authors.initials: R
authors.lastname: Atcher
authors.forename: J
authors.initials: J
authors.lastname: Humm