Preparation and use of NHS-MAG(3) for technetium-99m labeling of DNA

被引:110
作者
Winnard, P [1 ]
Chang, F [1 ]
Rusckowski, M [1 ]
Mardirossian, G [1 ]
Hnatowich, DJ [1 ]
机构
[1] UNIV MASSACHUSETTS, MED CTR, DEPT NUCL MED, WORCESTER, MA 01655 USA
关键词
amidothiols; chelator; mercaptoacetylglycylglycylglycine; Tc-99m;
D O I
10.1016/S0969-8051(97)00027-9
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
The chelator mercaptoacetylglycylglycylglycine (MAG(3)) is one of several amidothiols that have been used successfully to radiolabel proteins and other molecules with Tc-99m, Prior to radiolabeling, the sulfur in these amidothiols is usually protected by a benzoyl group (i.e. S-benzoyl MAG(3)) which requires extreme alkaline pH or boiling water temperatures for rapid deprotection, As a result, the benzoyl protected chelator is radiolabeled prior to conjugation (i.e. preconjugation labeling) in the case of carriers such as proteins or polypeptides which cannot withstand harsh conditions. We have employed a simple, two step, synthesis of the N- hydroxysuccinimide ester of MAG(3) in which the sulfur is protected with an acetyl group (i.e. S-acetyl NHS-MAG(3)). A single-stranded amine-derivitized DNA was coupled with NHS-S-acetyl MAG(3). Radiolabeling was accomplished at room temperature and neutral pH by transchelation from Tc-99m-tartrate. In comparison to labeled SHNH-DNA, the labeled MAG(3)-DNA was unstable to cysteine transchelation, however, in contrast to SHNH-DNA, no evidence for serum protein binding of the labeled MAG(3)-DNA was observed. We conclude that the S-acetyl NHS MAG(3) bifunctional chelator may prove to be an attractive alternative method of radiolabeling DNA and other biologically important molecules with Tc-99m. (C) 1997 Elsevier Science Inc.
引用
收藏
页码:425 / 432
页数:8
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