Closo-Dodecaborate(2-) as a Linker for Iodination of Macromolecules. Aspects on Conjugation Chemistry and Biodistribution

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• 作者：Vladimir Tolmachev ; Jacek Koziorowski ; Igor Sivaev ; Hans Lundqvist ; Jö ; rgen Carlsson ; Anna Orlova ; Lars Gedda ; Pä ; r Olsson ; Stefan Sjö ; berg ; and Anders Sundin
• 刊名：Bioconjugate Chemistry
• 出版年：1999
• 出版时间：May 1999
• 年：1999
• 卷：10
• 期：3
• 页码：338 - 345
• 全文大小：76K
• 年卷期：v.10,no.3(May 1999)
• ISSN：1520-4812

文摘

Boron-containing compounds like closo-dodecaborate(2-) are in theory suitable for radioactive labelingwith halogens. The boron-halogen bond is stronger than carbon-halogen bond and is not likely to berecognized by deiodinating enzymes in vivo. Peptides and proteins may be conjugated with variouscloso-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 conjugatesmay be directly labeled on the boron part with radioisotopes of iodine using the standard Chloramine-Tprocedure. Mercapto-undecahydro-closo-dodecaborate(2-) (BSH) was reacted with the double bond ofallyldextran to form a boronated dextran compound of the molecular size of about 70 kDa. Thiscompound, in the text denoted as Dx-BS, and cesium dodecahydro-closo-dodecaborate(2-) were labeledusing 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, asindicated by thyroid uptake, was found low. [¹²⁵I]Iodo-closo-dodecaborate(2-), which is a possibledegradation product of [¹²⁵I]Dx-BS-I, was rapidly excreted in urine without significant accumulationin any organ.