Closo-dodecaborate(2-) as a linker for iodination of macromolecules. Aspects on conjugation chemistry and biodistribution

Bioconjug Chem. 1999 May-Jun;10(3):338-45. doi: 10.1021/bc980033s.

Abstract

Boron-containing compounds like closo-dodecaborate(2-) are in theory suitable for radioactive labeling with halogens. The boron-halogen bond is stronger than carbon-halogen bond and is not likely to be recognized by deiodinating enzymes in vivo. Peptides and proteins may be conjugated with various closo-dodecaborate(2-)-containing ligands, and thereafter, the conjugate can be iodinated. Since closo-dodecaborate(2-) is more avidly iodinated than tyrosine in moderately acidic media, such conjugates may be directly labeled on the boron part with radioisotopes of iodine using the standard Chloramine-T procedure. Mercapto-undecahydro-closo-dodecaborate(2-) (BSH) was reacted with the double bond of allyldextran to form a boronated dextran compound of the molecular size of about 70 kDa. This compound, in the text denoted as Dx-BS, and cesium dodecahydro-closo-dodecaborate(2-) were labeled using iodine-125. The two compounds were administered to rats in order to study their in vivo stability. The results indicate that iodinated Dx-BS is stable for about 20 h in vivo. The degradation rate, as indicated by thyroid uptake, was found low. [125I]Iodo-closo-dodecaborate(2-), which is a possible degradation product of [125I]Dx-BS-I, was rapidly excreted in urine without significant accumulation in any organ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Boron Compounds / chemistry*
  • Boron Compounds / pharmacokinetics
  • Hydrogen-Ion Concentration
  • Iodine Radioisotopes / chemistry*
  • Iodine Radioisotopes / pharmacokinetics
  • Macromolecular Substances
  • Male
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Tyrosine / chemistry

Substances

  • Boron Compounds
  • Iodine Radioisotopes
  • Macromolecular Substances
  • Radiopharmaceuticals
  • dodecaborate
  • Tyrosine