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Preclinical Evaluat...
Preclinical Evaluation of a New Format of Ga-68- and In-111-Labeled Affibody Molecule Z(IGF-1R:4551) for the Visualization of IGF-1R Expression in Malignant Tumors Using PET and SPECT
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- Liu, Yongsheng (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Yu, Shengze (author)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, S-10044 Stockholm, Sweden.
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- Xu, Tianqi (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Bodenko, Vitalina (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Orlova, Anna (author)
- Uppsala universitet,Theranostics,Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Oroujeni, Maryam, PhD, 1982- (author)
- Uppsala universitet,Medicinsk strålningsvetenskap,Affibody AB, S-17165 Solna, Sweden.
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- Rinne, Sara S. (author)
- Uppsala universitet,Theranostics
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Medicinsk strålningsvetenskap,Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Vorobyeva, Anzhelika (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Gräslund, Torbjörn, 1970- (author)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, S-10044 Stockholm, Sweden.
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(creator_code:org_t)
- 2022-07-15
- 2022
- English.
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In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:7
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Abstract
Subject headings
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- The Insulin-like growth factor-1 receptor (IGF-1R) is a molecular target for several monoclonal antibodies undergoing clinical evaluation as anticancer therapeutics. The non-invasive detection of IGF-1R expression in tumors might enable stratification of patients for specific treatment and improve the outcome of both clinical trials and routine treatment. The affibody molecule Z(IGF-1R:4551) binds specifically to IGF-1R with subnanomolar affinity. The goal of this study was to evaluate the Ga-68 and In-111-labeled affibody construct NODAGA-(HE)(3)-Z(IGF-1R:4551) for the imaging of IGF-1R expression, using PET and SPECT. The labeling was efficient and provided stable coupling of both radionuclides. The two imaging probes, [Ga-68]Ga-NODAGA-(HE)(3)-Z(IGF-1R:4551) and [In-111]In-NODAGA-(HE)(3)-Z(IGF-1R:4551), demonstrated specific binding to IGF-1R-expressing human cancer cell lines in vitro and to IGF-1R-expressing xenografts in mice. Preclinical PET and SPECT/CT imaging demonstrated visualization of IGF-1R-expressing xenografts already one hour after injection. The tumor-to-blood ratios at 3 h after injection were 7.8 +/- 0.2 and 8.0 +/- 0.6 for [Ga-68]Ga-NODAGA-(HE)(3)-Z(IGF-1R:4551) and [In-111]In-NODAGA-(HE)(3)-Z(IGF-1R:4551), respectively. In conclusion, a molecular design of the Z(IGF-1R:4551) affibody molecule, including placement of a (HE)(3)-tag on the N-terminus and site-specific coupling of a NODAGA chelator on the C-terminus, provides a tracer with improved imaging properties for visualization of IGF-1R in malignant tumors, using PET and SPECT.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Keyword
- IGF-1R
- PET
- SPECT
- gallium-68
- indium-111
- affibody molecules
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Liu, Yongsheng
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Yu, Shengze
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Xu, Tianqi
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Bodenko, Vitalin ...
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Orlova, Anna
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Oroujeni, Maryam ...
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Rinne, Sara S.
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Tolmachev, Vladi ...
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Vorobyeva, Anzhe ...
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Gräslund, Torbjö ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Radiology Nuclea ...
- Articles in the publication
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Pharmaceutics
- By the university
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Royal Institute of Technology
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Uppsala University