THE USE OF PB-212-LABELED MONOCLONAL-ANTIBODY IN THE TREATMENT OF MURINE ERYTHROLEUKEMIA

Purpose: The goals of this study were to learn whether the DOTA chelat or was useful for targeting lead radionuclides (Pb-203,Pb-212) to cell s and tissues invaded by the Rauscher leukemia virus (RVB3) and to inv estigate the therapeutic efficacy of targeted Pb-212 in treating the m urine leukemia. Methods and Materials: Five to 6-week-old BALB/c mice were inoculated i.v. with RVB3, This virus causes marked splenomegaly and death by day 13 and day 70 postinfection, respectively, Biodistrib ution, tumor targeting, and toxicity studies were performed using vary ing doses of Pb-212-DOTA-103A. A heavy metal chelator, DMPS, was admin istered orally and parenterally in two phases of the toxicity study. R esults: Biodistribution studies showed marked tumor targeting (58% ID/ g spleen) in mice treated with Pb-203-103A as compared to mice treated with control antibody B3 (4.6% ID/g spleen), Histologic cure was achi eved in all leukemic mice treated with 20 mu Ci Pb-212-103A; however, all of the mice died with leukopenia and secondary bacterial infection s due to severe bone marrow toxicity. Nonleukemic mice and mice treate d with 20 mu Ci Pb-212-B3 experienced less marrow toxicity and longer survival, Coadministration of the heavy metal chelator did not diminis h the bone marrow toxicity. Conclusion: An effective, nonlethal dose c ould not be established to treat this tumor, The severe bone marrow to xicity associated with this radionuclide may limit its usefulness in s ystemic radioimmunotherapy.