化合价和标记化学对使用放射性碘化HER2结合亲和体分子进行体内靶向的影响。
Influence of valency and labelling chemistry on in vivo targeting using radioiodinated HER2-binding Affibody molecules.
作者信息
Tolmachev Vladimir, Mume Eskender, Sjöberg Stefan, Frejd Fredrik Y, Orlova Anna
机构信息
Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
出版信息
Eur J Nucl Med Mol Imaging. 2009 Apr;36(4):692-701. doi: 10.1007/s00259-008-1003-y. Epub 2008 Dec 10.
PURPOSE
HER2 is a transmembrane tyrosine kinase, which is overexpressed in a number of carcinomas. The Affibody molecule Z(HER2:342) is a small (7 kDa) affinity protein binding to HER2 with an affinity of 22 pM. The goal of this study was to evaluate the use of ((4-hydroxyphenyl)ethyl)maleimide (HPEM) for radioiodination of Z(HER2:342) and to compare the targeting properties of monomeric and dimeric forms of Z(HER2:342).
METHODS
The biodistribution of different radioiodinated derivatives of Z(HER2:342) was studied in BALB/C nu/nu mice bearing HER2-expressing SKOV-3 xenografts. Biodistributions of (125)I-PIB-Z(HER2:342) and site-specifically labelled (125)I-HPEM-Z(HER2:342)-C were compared. Biodistributions of monomeric (131)I-HPEM-Z(HER2:342)-C and dimeric (125)I-HPEM-(Z(HER2:342))(2)-C were evaluated using a paired-label method.
RESULTS
(125)I-HPEM-Z(HER2:342)-C had the same level of tumour accumulation as (125)I-PIB-Z(HER2:342), but fourfold lower renal retention of radioactivity. The monomeric form of Z(HER2:342) provided better tumour targeting than the dimeric form.
CONCLUSION
Favourable biodistribution of (131)I-HPEM-Z(HER2:342)-C makes it a promising candidate for radionuclide therapy.
目的
HER2是一种跨膜酪氨酸激酶，在多种癌症中过表达。亲和体分子Z(HER2:342)是一种小的（7 kDa）亲和蛋白，与HER2的亲和力为22 pM。本研究的目的是评估((4-羟基苯基)乙基)马来酰亚胺（HPEM）用于Z(HER2:342)放射性碘化的效果，并比较Z(HER2:342)单体和二聚体形式的靶向特性。
方法
在携带表达HER2的SKOV-3异种移植瘤的BALB/C nu/nu小鼠中研究了Z(HER2:342)不同放射性碘化衍生物的生物分布。比较了(125)I-PIB-Z(HER2:342)和位点特异性标记的(125)I-HPEM-Z(HER2:342)-C的生物分布。使用配对标记法评估了单体(131)I-HPEM-Z(HER2:342)-C和二聚体(125)I-HPEM-(Z(HER2:342))(2)-C的生物分布。
结果
(125)I-HPEM-Z(HER2:342)-C的肿瘤蓄积水平与(125)I-PIB-Z(HER2:342)相同，但肾脏放射性滞留降低了四倍。Z(HER2:342)的单体形式比二聚体形式具有更好的肿瘤靶向性。
结论
(131)I-HPEM-Z(HER2:342)-C良好的生物分布使其成为放射性核素治疗的有前景的候选药物。
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