文章基本信息

标题：Improved contrast of affibody-mediated imaging of HER3 expression in mouse xenograft model through co-injection of a trivalent affibody for in vivo blocking of hepatic uptake
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作者：Maria Rosestedt ; Ken G. Andersson ; Sara S. Rinne 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-10
DOI：10.1038/s41598-019-43145-2
出版社：Springer Nature
摘要：Human epidermal growth factor receptor type 3 (HER3) plays a crucial role in the progression of many cancer types. In vivo radionuclide imaging could be a reliable method for repetitive detection of HER3-expression in tumors. The main challenge of HER3-imaging is the low expression in tumors together with endogenous receptor expression in normal tissues, particularly the liver. A HER3-targeting affibody molecule labeled with radiocobalt via a NOTA chelator [ 57 Co]Co-NOTA-Z 08699 has demonstrated the most favorable biodistribution profile with the lowest unspecific hepatic uptake and high activity uptake in tumors. We hypothesized that specific uptake of labeled affibody monomer might be selectively blocked in the liver but not in tumors by a co-injection of non-labeled corresponding trivalent affibody (Z 08699 ) 3 . Biodistribution of [ 57 Co]Co-NOTA-Z 08699 and [ 111 In]In-DOTA-(Z 08699 ) 3 was studied in BxPC-3 xenografted mice. [ 57 Co]Co-NOTA-Z 08699 was co-injected with unlabeled trivalent affibody DOTA-(Z 08699 ) 3 at different monomer:trimer molar ratios. HER3-expression in xenografts was imaged using [ 57 Co]Co-NOTA-Z 08699 and [ 57 Co]Co-NOTA-Z 08699 : DOTA-(Z 08699 ) 3 . Hepatic activity uptake of [ 57 Co]Co-NOTA-Z 08699 : DOTA-(Z 08699 ) 3 decreased with increasing monomer:trimer molar ratio. The tumor activity uptake and tumor-to-liver ratios were the highest for the 1:3 ratio. SPECT/CT images confirmed the biodistribution data. Imaging of HER3 expression can be improved by co-injection of a radiolabeled monomeric affibody-based imaging probe together with a trivalent affibody.