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

Boron-containing compounds like closo-dodecaborate(2-) are in theory suitab le for radioactive labeling with halogens. The boron-halogen bond is strong er than carbon-halogen bond and is not likely to be recognized by deiodinat ing enzymes in vivo. Peptides and proteins may be conjugated with various c loso-dodecaborate(2-)-containing ligands, and thereafter, the conjugate can be iodinated. Since closo-dodecaborate(2-) is more avidly iodinated than t yrosine in moderately acidic media, such conjugates may be directly labeled on the boron part with radioisotopes of iodine using the standard Chlorami ne-T procedure. Mercapto-undecahydro-closo-dodecaborate(2-) (BSH) was react ed with the double bond of allyldextran to form a boronated dextran compoun d 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 stabl e for about 20 h in vivo. The degradation rate, as indicated by thyroid upt ake, was found low. [I-125]Iodo-closo-dodecaborate(2-), which is a possible degradation product of[I-125]DX-BS-I, was rapidly excreted in urine withou t significant accumulation in any organ.