G Ruble1, C Wu, R A Squire, O A Ganswo, M Strand. 1. Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205. USA.
Abstract
PURPOSE: The goals of this study were to learn whether the DOTA chelator was useful for targeting lead radionuclides (203,212 Pb) to cells and tissues invaded by the Rauscher leukemia virus (RVB3) and to investigate the therapeutic efficacy of targeted 212Pb in treating the murine 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. Biodistribution, tumor targeting, and toxicity studies were performed using varying doses of 212Pb-DOTA-103A. A heavy metal chelator, DMPS, was administered orally and parenterally in two phases of the toxicity study. RESULTS: Biodistribution studies showed marked tumor targeting (58% ID/g spleen) in mice treated with 203Pb-103A as compared with mice treated with control antibody B3 (4.6% ID/g spleen). Histologic cure was achieved in all leukemic mice treated with 20 muCi212Pb-103A; however, all of the mice died with leukopenia and secondary++ bacterial infections due to severe bone marrow toxicity. Nonleukemic mice and mice treated with 20 muCi212Pb-B3 experienced less marrow toxicity and longer survival. Coadministration of the heavy metal chelator did not diminish the bone marrow toxicity. CONCLUSION: An effective, nonlethal dose could not be established to treat this tumor. The severe bone marrow toxicity associated with this radionuclide may limit its usefulness in systemic radioimmunotherapy.
PURPOSE: The goals of this study were to learn whether the DOTA chelator was useful for targeting lead radionuclides (203,212 Pb) to cells and tissues invaded by the Rauscher leukemia virus (RVB3) and to investigate the therapeutic efficacy of targeted 212Pb in treating the murineleukemia. 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. Biodistribution, tumor targeting, and toxicity studies were performed using varying doses of 212Pb-DOTA-103A. A heavy metal chelator, DMPS, was administered orally and parenterally in two phases of the toxicity study. RESULTS: Biodistribution studies showed marked tumor targeting (58% ID/g spleen) in mice treated with 203Pb-103A as compared with mice treated with control antibody B3 (4.6% ID/g spleen). Histologic cure was achieved in all leukemicmice treated with 20 muCi212Pb-103A; however, all of the mice died with leukopenia and secondary++ bacterial infections due to severe bone marrow toxicity. Nonleukemic mice and mice treated with 20 muCi212Pb-B3 experienced less marrow toxicity and longer survival. Coadministration of the heavy metal chelator did not diminish the bone marrow toxicity. CONCLUSION: An effective, nonlethal dose could not be established to treat this tumor. The severe bone marrow toxicity associated with this radionuclide may limit its usefulness in systemic radioimmunotherapy.
Authors: Hyun A Song; Chi Soo Kang; Kwamena E Baidoo; Diane E Milenic; Yunwei Chen; Anzhi Dai; M W Brechbiel; Hyun-Soon Chong Journal: Bioconjug Chem Date: 2011-05-23 Impact factor: 4.774
Authors: John M Pagel; Frederick R Appelbaum; Janet F Eary; Joseph Rajendran; Darrell R Fisher; Ted Gooley; Katherine Ruffner; Eneida Nemecek; Eileen Sickle; Larry Durack; Jeanette Carreras; Mary M Horowitz; Oliver W Press; Ajay K Gopal; Paul J Martin; Irwin D Bernstein; Dana C Matthews Journal: Blood Date: 2005-10-27 Impact factor: 22.113