title: Closo-dodecaborate(2-) as a linker for iodination of macromolecules. Aspects on conjugation chemistry and biodistribution.
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.
authors.affiliation: Division of Biomedical Radiation Sciences, Box 535, S-751 21, Uppsala University, Uppsala, Sweden. Vladimir.Tolmachev@bms.uu.se
authors.forename: V
authors.initials: V
authors.lastname: Tolmachev
authors.forename: J
authors.initials: J
authors.lastname: Koziorowski
authors.forename: I
authors.initials: I
authors.lastname: Sivaev
authors.forename: H
authors.initials: H
authors.lastname: Lundqvist
authors.forename: J
authors.initials: J
authors.lastname: Carlsson
authors.forename: A
authors.initials: A
authors.lastname: Orlova
authors.forename: L
authors.initials: L
authors.lastname: Gedda
authors.forename: P
authors.initials: P
authors.lastname: Olsson
authors.forename: S
authors.initials: S
authors.lastname: Sjöberg
authors.forename: A
authors.initials: A
authors.lastname: Sundin
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007457:Iodine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D046911:Macromolecular Substances; D008297:Male; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014443:Tyrosine / Q000737:chemistry
chemical_list: D001896:Boron Compounds; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D019275:Radiopharmaceuticals; C119788:dodecaborate; D014443:Tyrosine