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Imaging of Insulinl...
Imaging of Insulinlike Growth Factor Type 1 Receptor in Prostate Cancer Xenografts Using the Affibody Molecule (111)In-DOTA-Z(IGF1R:4551)
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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- Malmberg, Jennie (author)
- Uppsala universitet,Plattformen för preklinisk PET,Anna Orlova
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- Hofström, Camilla (author)
- KTH,Molekylär Bioteknologi
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Abrahmsén, Lars (author)
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Bergman, Thomas (author)
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Sjöberg, Anna (author)
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- Sandström, Mattias (author)
- Uppsala universitet,Enheten för onkologi,Enheten för radiologi
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- Gräslund, Torbjörn (author)
- KTH,Molekylär Bioteknologi
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- Orlova, Anna (author)
- Uppsala universitet,Plattformen för preklinisk PET,Anna Orlova
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(creator_code:org_t)
- 2011-12-15
- 2012
- English.
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 53:1, s. 90-97
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Abstract
Subject headings
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- One of the pathways leading to androgen independence in prostate cancer involves upregulation of insulinlike growth factor type 1 receptor (IGF-1R). Radionuclide imaging of IGF-1R in tumors might be used for selection of patients who would most likely benefit from IGF-1R-targeted therapy. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of IGF-1R expression in prostate cancer xenografts using a small nonimmunoglobulin-derived binding protein called an Affibody molecule. Methods: The IGF-1R-binding Z(IGF1R:4551) Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with (111)In. The binding of radiolabeled Z(IGF1R:4551) to IGF-1R-expressing cells was evaluated in vitro and in vivo. Results: DOTA-Z(IGF1R:4551) can be stably labeled with (111)In with preserved specific binding to IGF-1R-expressing cells in vitro. In mice, (111)In-DOTAZ(IGF1R):(4551) accumulated in IGF-1R-expressing organs (pancreas, stomach, lung, and salivary gland). Receptor saturation experiments demonstrated that targeting of DU-145 prostate cancer xenografts in NMRI nu/nu mice was IGF-1R-specific. The tumor uptake was 1.1 +/- 0.3 percentage injected dose per gram, and the tumor-to-blood ratio was 3.2 +/- 0.2 at 8 h after injection. Conclusion: This study demonstrates the feasibility of in vivo targeting of IGF-1R-expressing prostate cancer xenografts using an Affibody molecule. Further development of radiolabeled Affibody molecules might provide a useful clinical tool for stratification of patients with prostate cancer for IGF-1R-targeting therapy.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Affibody molecule
- (111)In
- molecular imaging
- IGF-1R
- DU145 xenograft
Publication and Content Type
- ref (subject category)
- art (subject category)
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