Synthesis, metal chelate stability studies, enzyme digestion of a peptide-linked DOTA derivative and its corresponding radiolabeled immunoconjugates

Min Li, Claude F. Meares

Research output: Contribution to journalArticle

108 Scopus citations


By directly coupling a tetrapeptide to DOTA through an amide bond, we synthesized a novel DOTA derivative, DOTA-glycylglycylglycyl-L-p-nitrophenylalanine amide. We converted this new precursor bifunctional chelating agent to DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine and conjugated it to monoclonal antibody Lym-1. Serum stability studies show that the radiolabeled conjugates are kinetically inert under physiological conditions. The rates of loss of radiometals in human serum are 0.1 ± 0.1% per day for InIII, 0.02 ± 0.15% per day for YIII, and 0.3 ± 0.2% per day for CuII labeled immunoconjugates. In the presence of the liver enzyme cathepsin B, an in vitro digestion of 114mIn-labeled conjugate yields a small fragment containing 114mIn. Characterization of the cleavage products shows that this liver enzyme hydrolyzes the peptide linkage before the phenylalanine residue, freeing the In-DOTA-triglycine complex from the conjugate. However, the liver enzyme cathepsin D does not cleave the linkage over the span of 7 days.

Original languageEnglish (US)
Pages (from-to)275-283
Number of pages9
JournalBioconjugate Chemistry
Issue number4
StatePublished - 1993


ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

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