Linked Life Data

8242624

Source:http://linkedlifedata.com/resource/pubmed/id/8242624

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
1994-1-3
pubmed:abstractText
A major factor that is critical to the potential effectiveness of alpha-emitter 212Bi radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. The chelate should bind the radiometal firmly to minimize release of the radionuclide from the monoclonal antibody-chelate complex. The present study examines a member of a new class of polyamine carboxylate chelating compounds, the DOTA ligands, for conjugating radiometal ions to antibody. Biocompatibility and stability are assessed with the anti-Tac monoclonal antibody that is directed against the human interleukin 2 receptors. The scientific basis for the clinical use of this antibody in radioimmunotherapy is that resting normal cells do not express the interleukin 2 receptor, whereas the receptor is expressed on the surface of certain neoplasms and by activated T-cells in select autoimmune diseases and in allograft rejection. First, we examined the impact of the labeling procedure and the presence of the chelate, DOTA, on antibody bioavailability and survival. Next, we studied the capacity of the antibody-chelate complex to retain radiobismuth. Coupling DOTA to antibody or adding Bi(III) to DOTA-coupled antibody did not disturb antibody immunoreactivity in in vitro binding studies. In addition, as analyzed by in vivo studies, DOTA-antibody dummy labeled with nonradioactive bismuth showed pharmacokinetics and tissue distribution identical to those of antibody not modified with DOTA. DOTA-anti-Tac charged with radioactive bismuth showed pharmacokinetics identical to radioiodinated dummy-labeled DOTA-antibody, suggesting little premature release of radioactive bismuth from the antibody complex. Moreover, in the early, therapeutically relevant time points (2 h and 6 h), there was no significant preferential accumulation of bismuth in any organ. At the 5-day time point, beyond the range of therapeutic interest, there was delayed excretion of bismuth from reticuloendothelial tissues relative to radioiodine from catabolized antibody. Excretion of catabolized DOTA-bismuth had an apparent t1/2 of approximately 1 day without the marked renal accumulation typical of the free bismuth ion. The compatibility of DOTA conjugation with antibody bioactivity and the stability of the radioactive bismuth complex in vivo provide important preclinical validation of the potential utility of this new chelating agent for 212Bi monoclonal antibody radioimmunotherapy in humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5683-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Pharmacokinetics and bioactivity of 1,4,7,10-tetra-azacylododecane off',N'',N'''-tetraacetic acid (DOTA)-bismuth-conjugated anti-Tac antibody for alpha-emitter (212Bi) therapy.
pubmed:affiliation
Division of Hematology-Oncology, Harvard Medical School, New England Deaconess Hospital, Boston, Massachusetts 02215.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't