Conjugation of DOTA Using Isolated Phenolic Active Esters: The Labeling and Biodistribution of Albumin as Blood Pool Marker

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• 作者：Walter Mier ; Johannes Hoffend ; Susanne Krä ; mer ; Jochen Schuhmacher ; William E. Hull ; Michael Eisenhut ; and Uwe Haberkorn
• 刊名：Bioconjugate Chemistry
• 出版年：2005
• 出版时间：January 2005
• 年：2005
• 卷：16
• 期：1
• 页码：237 - 240
• 全文大小：149K
• 年卷期：v.16,no.1(January 2005)
• ISSN：1520-4812

文摘

A convenient method for the functionalization of proteins with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) has been developed. For this purpose DOTA was converted into a series ofdifferent monoreactive activated phenolic esters. The esters were prepared in a single step fromcommercially available DOTA, using 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide or 1,3-dicyclohexylcarbodiimide as coupling agent. The resulting activated esters were isolated by HPLC, lyophilized,and stored for future applications. In solid form the compounds exhibit high hydrolytic stability. Thereactions with proteins proceeded in good yields. The conjugation and subsequent radiolabeling ofthe 4-nitrophenol ester of DOTA with ⁶⁷Ga was investigated with rat serum albumin. A time-dependentbiodistribution study in tumor bearing rats was conducted to demonstrate the integrity of the albuminconjugate. These results suggest that phenolic esters of DOTA represent versatile reagents to conjugateDOTA with proteins and other biomolecules in high yields.