Chelate radiochemistry: Cleavable linkers lead to altered levels of radioactivity in the liver

Claude F. Meares, Michael J. McCall, Shrikant V. Deshpande, Sally J. Denardo, David A. Goodwin

Research output: Contribution to journalArticle

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Abstract

Bifunational chelating agents based on benzyl‐EDTA bind IIIIn 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 IIIIn 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 IIIIn 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 IIIIn 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.

Original languageEnglish (US)
Pages (from-to)99-102
Number of pages4
JournalInternational Journal of Cancer
Volume41
Issue number2 S
DOIs
StatePublished - 1988

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ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Meares, C. F., McCall, M. J., Deshpande, S. V., Denardo, S. J., & Goodwin, D. A. (1988). Chelate radiochemistry: Cleavable linkers lead to altered levels of radioactivity in the liver. International Journal of Cancer, 41(2 S), 99-102. https://doi.org/10.1002/ijc.2910410723