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Comparative toxicity studies of yttrium‐90 mx‐dtpa and 2‐it‐bad conjugated monoclonal antibody (bre‐3)
Author(s) -
Denardo G. L.,
Kroger L. A.,
Denardo S. J.,
Miers L. A.,
Salako Q.,
Kukis D. L.,
Fand I.,
Shen S.,
Renn O.,
Meares C. F.
Publication year - 1994
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19940201)73:3+<1012::aid-cncr2820731340>3.0.co;2-0
Subject(s) - radioimmunotherapy , toxicity , bone marrow , medicine , skeleton (computer programming) , therapeutic index , monoclonal antibody , chelation , nuclear medicine , radiochemistry , cancer research , pharmacology , antibody , pathology , immunology , chemistry , anatomy , drug , organic chemistry
Background . BrE‐3 is a monoclonal antibody that has promise for imaging and therapy of human adenocarcinoma. Because of observations in therapeutic trials of yttrium‐90 ( 90 Y) escape from radioimmunoconjugates and uptake by the skeleton with resultant bone marrow toxicity, the authors attempted to evaluate the importance of this factor by a comparison of the LD 50 in healthy mice treated with 90 Y that had been chelated with either of two high affinity chelators, methylbenzyldiethylene‐triaminepentaacetic acid (MX‐DTPA) or bromoacetamidobenzyl‐1,4,7,10‐tetraazocyclododecane‐N,N′,N″,N″‐tetraacetic acid (BAD). Methods and Results . Bone marrow hematopoietic toxicity was dose‐limiting and the source of death for both chelators. The LD 50 for 90 Y‐BrE‐3‐MX‐DTPA was 220.9 μCi, and that for 90 Y‐BrE‐3‐2IT‐BAD was 307.8 μCi. Whole‐body autoradiography revealed substantially greater uptake of 90 Y in the skeleton when MX‐DTPA was used as the chelator. Conclusions . These observations suggest that 90 Y escape to bone is a significant factor in the maximum tolerated dose of radioimmunoconjugate that can be used in therapeutic trials. These results probably underestimate the importance of 90 Y escape since 90 Y in the skeleton of patients is likely to be more significant than in mice because more of the 90 Y energy is absorbed in the marrow of larger species. Cancer 1994 73:1012–22.