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Chelate radiochemistry: Cleavable linkers lead to altered levels of radioactivity in the liver
Author(s) -
Meares Claude F.,
McCall Michael J.,
Deshpande Shrikant V.,
Denardo Sally J.,
Goodwin David A.
Publication year - 1988
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910410723
Subject(s) - biodistribution , conjugate , linker , chelation , chemistry , dota , thioether , clearance , bifunctional , combinatorial chemistry , peptide , thiourea , covalent bond , stereochemistry , biochemistry , organic chemistry , in vitro , medicine , mathematical analysis , mathematics , computer science , urology , operating system , catalysis
Bifunational chelating agents based on benzyl‐EDTA bind III In stably under physiological conditions. Available evidence indicates that the indium is cleared from the body in its original chelated form. Initial studies of a series of antibody‐chelate conjugates joined by different molecular linkers show that the III In biodistribution is strongly dependent on the nature of the linker. Linkers containing thiourea, thioether, peptide, ester, and disulfide groups were compared in healthy BALB/c mice. The disulfide linker led to particularly rapid clearance of III In from the liver, and from the whole body. Results did not appear to be as favorable as those currently obtainable with reversible radiolabelling techniques, in which the III In chelate is bound non‐covalently to the antibody and a competing hapten is used to displace it when desired. However, the concept of a metabolically cleavable linker is sound. Further exploration is needed to produce a conjugate with the desired properties.