The use of 212Pb-labeled monoclonal antibody in the treatment of murine erythroleukemia.
OBJECTIVE
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
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.


CONCLUSIONS
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.
Ruble
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G
Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205. USA.
Wu
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C
Squire
R A
RA
Ganswo
O A
OA
Strand
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D000918:Antibody Specificity; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004355:Drug Stability; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D007856:Lead Radioisotopes / Q000627:therapeutic use*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D014494:Unithiol / Q000494:pharmacology
C087160:2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid; D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D006571:Heterocyclic Compounds; D000922:Immunotoxins; D017879:Isothiocyanates; D007856:Lead Radioisotopes; D014494:Unithiol