Evaluation of 99mTc-ZIGF1R:4551-GGGC affibody molecule, a new probe for imaging of insulin-like growth factor type 1 receptor expression

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• 作者：Bogdan Mitran ; Mohamed Altai ; Camilla Hofstr?m ; Hadis Honarvar…
• 关键词：Affibody molecule ; IGF ; 1R ; Peptide ; based chelator ; 99mTc ; Biodistribution
• 刊名：Amino Acids
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：47
• 期：2
• 页码：303-315
• 全文大小：660 KB
• 参考文献：1. Ahlgren S, Tolmachev V (2010) Radionuclide molecular imaging using Affibody molecules. Curr Pharm Biotechnol 11:581-89 CrossRef
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  4. Ahlgren S, Andersson K, Tolmachev V (2010) Kit formulation for 99mTc-labeling of recombinant anti-HER2 Affibody molecules with a C-terminally engineered cysteine. Nucl Med Biol 37:539-46 CrossRef
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• 作者单位：Bogdan Mitran (1)
  Mohamed Altai (2)
  Camilla Hofstr?m (3)
  Hadis Honarvar (2)
  Mattias Sandstr?m (4)
  Anna Orlova (1)
  Vladimir Tolmachev (2)
  Torbj?rn Gr?slund (3)
  
  1. Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
  2. Unit of Biomedical Radiation Sciences, Department of Radiology, Oncology, and Radiation Sciences, Rudbeck Laboratory, Uppsala University, 751 85, Uppsala, Sweden
  3. Division of Protein Technology, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden
  4. Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden
  
• 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

Overexpression of insulin-like growth factor-1 receptor (IGF-1R) in several cancers is associated with resistance to therapy. Radionuclide molecular imaging of IGF-1R expression in tumors may help in selecting the patients that will potentially respond to IGF-1R-targeted therapy. Affibody molecules are small (7?kDa) non-immunoglobulin-based scaffold proteins that are well-suited probes for radionuclide imaging. The aim of this study was the evaluation of an anti-IGF-1R affibody molecule labeled with technetium-99m using cysteine-containing peptide-based chelator GGGC at C-terminus. ZIGF1R:4551-GGGC was efficiently and stably labeled with technetium-99m (radiochemical yield 97?±?3?%). 99mTc-ZIGF1R:4551-GGGC demonstrated specific binding to IGF-1R-expressing DU-145 (prostate cancer) and MCF-7 (breast cancer) cell lines and slow internalization in vitro. The tumor-targeting properties were studied in BALB/c nu/nu mice bearing DU-145 and MCF-7 xenografts. [99mTc(CO)3]+-(HE)3-ZIGF1R:4551 was used for comparison. The biodistribution study demonstrated high tumor-to-blood ratios (6.2?±?0.9 and 6.9?±?1.0, for DU-145 and MCF-7, respectively, at 4?h after injection). Renal radioactivity concentration was 16-fold lower for 99mTc-ZIGF1R:4551-GGGC than for [99mTc(CO)3]+-(HE)3-ZIGF1R:4551 at 4?h after injection. However, the liver uptake of 99mTc-ZIGF1R:4551-GGGC was 1.2- to 2-fold higher in comparison with [99mTc(CO)3]+-(HE)3-ZIGF1R:4551. A possible reason for the elevated hepatic uptake of 99mTc-ZIGF1R:4551-GGGC is a high lipophilicity of amino acids in the binding site of ZIGF1R:4551, which is not compensated in 99mTc-ZIGF1R:4551-GGGC. In conclusion, 99mTc-ZIGF1R:4551-GGGC can visualize the IGF-1R expression in human tumor xenografts and provides low retention of radioactivity in kidneys. Further development of this imaging agent should include molecular design aimed at reducing the hepatic uptake.