使用N-琥珀酰亚胺基4-羟基-3-碘苯甲酸酯对蛋白质进行放射性碘化。

Radioiodination of proteins using N-succinimidyl 4-hydroxy-3-iodobenzoate.

作者信息

Vaidyanathan G, Affleck D J, Zalutsky M R

机构信息

Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.

出版信息

Bioconjug Chem. 1993 Jan-Feb;4(1):78-84. doi: 10.1021/bc00019a011.

DOI:10.1021/bc00019a011

PMID:8431515

Abstract

N-Succinimidyl 4-hydroxy-3-[131I]iodobenzoate ([131I]SHIB) was synthesized from 4-hydroxybenzoic acid in two steps. The overall radiochemical yield was 40-56%. A monoclonal antibody (mAb) was labeled in 10-15% yield by reaction with [131I]SHIB. The specific binding of [131I]SHIB mAb to tumor homogenates in vivo was 78 +/- 3%, compared to 84 +/- 3% for the same mAb labeled using N-succinimidyl 3-[125I]iodobenzoate ([125I]SIB). Paired-label studies in normal mice demonstrated similar tissue distributions of 131I and 125I except in thyroid. In thyroid, uptake of the two isotopes was similar on day 1; however, 131I levels increased gradually to 2-3 times those of 125I by day 6. Our results indicate that loss of label in vivo from mAbs labeled using SHIB is somewhat higher than seen with SIB but significantly lower than that observed when direct iodination methods are used.

摘要

N-琥珀酰亚胺基4-羟基-3-[¹³¹I]碘苯甲酸酯（[¹³¹I]SHIB）由4-羟基苯甲酸分两步合成。总放射化学产率为40 - 56%。通过与[¹³¹I]SHIB反应，单克隆抗体（mAb）的标记产率为10 - 15%。[¹³¹I]SHIB mAb在体内与肿瘤匀浆的特异性结合率为78±3%，而使用N-琥珀酰亚胺基3-[¹²⁵I]碘苯甲酸酯（[¹²⁵I]SIB）标记的同一mAb的特异性结合率为84±3%。正常小鼠的配对标记研究表明，除甲状腺外，¹³¹I和¹²⁵I的组织分布相似。在甲状腺中，两种同位素在第1天的摄取相似；然而，到第6天，¹³¹I水平逐渐增加到¹²⁵I的2 - 3倍。我们的结果表明，使用SHIB标记的mAb在体内的标记损失略高于使用SIB，但明显低于使用直接碘化方法时观察到的损失。