PET imaging of insulin-like growth factor type 1 receptor expression with a 64Cu-labeled Affibody molecule

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• 作者：Xinhui Su ; Kai Cheng ; Yang Liu ; Xiang Hu ; Shuxian Meng ; Zhen Cheng
• 关键词：Affibody ; IGF ; 1R ; PET ; 64Cu ; NOTA
• 刊名：Amino Acids
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：47
• 期：7
• 页码：1409-1419
• 全文大小：755 KB
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  Rolleman EJ, de Val
• 作者单位：Xinhui Su (1) (2)
  Kai Cheng (2)
  Yang Liu (2)
  Xiang Hu (2)
  Shuxian Meng (2)
  Zhen Cheng (2)
  
  1. Department of Nuclear Medicine, Zhongshan Hospital Xiamen University, Xiamen, China
  2. Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Bio-X Program and Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA, 94305, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Analytical Chemistry
  Biochemical Engineering
  Life Sciences
  Proteomics
  Neurobiology
  
• 出版者：Springer Wien
• ISSN：1438-2199

文摘

The insulin-like growth factor 1 receptor (IGF-1R) serves as an attractive target for cancer molecular imaging and therapy. Previous single photon emission computerized tomography (SPECT) studies showed that the IGF-1R-targeting Affibody molecules 99mTc-Z_IGF1R:4551-GGGC, [99mTc(CO)₃]+-(HE)₃-Z_IGF1R:4551 and 111In-DOTA-Z_IGF1R:4551 can discriminate between high and low IGF-1R-expression tumors and have the potential for patient selection for IGF-1R-targeted therapy. Compared with SPECT, positron emission tomography (PET) may improve imaging of IGF-1R-expression, because of its high sensitivity, high spatial resolution, strong quantification ability. The aim of the present study was to develop the 64Cu-labeled NOTA-conjugated Affibody molecule Z_IGF-1R:4:40 as a PET probe for imaging of IGF-1R-positive tumor. An Affibody analogue (Ac-Cys-Z_IGF-1R:4:40) binding to IGF-1R was site-specifically conjugated with NOTA and labeled with 64Cu. Binding affinity and specificity of 64Cu-NOTA-Z_IGF-1R:4:40 to IGF-1R were evaluated using human glioblastoma U87MG cells. Small-animal PET, biodistribution, and metabolic stability studies were conducted on mice bearing U87MG xenografts after the injection of 64Cu-NOTA-Z_IGF-1R:4:40 with or without co-injection of unlabeled Affibody proteins. The radiosynthesis of 64Cu-NOTA-Z_IGF-1R:4:40 was completed successfully within 60?min with a decay-corrected yield of 75?%. 64Cu-NOTA-Z_IGF-1R:4:40 bound to IGF-1R with low nanomolar affinity (K _D?=?28.55?±?3.95?nM) in U87MG cells. 64Cu-NOTA-Z_IGF-1R:4:40 also displayed excellent in vitro and in vivo stability. In vivo biodistribution and PET studies demonstrated targeting of U87MG gliomas xenografts was IGF-1R specific. The tumor uptake was 5.08?±?1.07?%ID/g, and the tumor to muscle ratio was 11.89?±?2.16 at 24?h after injection. Small animal PET imaging studies revealed that 64Cu-NOTA-Z_IGF-1R:4:40 could clearly identify U87MG tumors with good contrast at 1-4?h after injection. This study demonstrates that 64Cu-NOTA-Z_IGF-1R:4:40 is a promising PET probe for imaging IGF-1R positive tumor.