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Comparative evaluat...
Comparative evaluation of affibody- and antibody fragments-based CAIX imaging probes in mice bearing renal cell carcinoma xenografts
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- Garousi, Javad (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Huizing, Fokko J. (author)
- Radboud Univ Nijmegen, Dept Radiat Oncol, Med Ctr, Nijmegen, Netherlands.
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- Vorobyeva, Anzhelika (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Mitran, Bogdan (author)
- Uppsala universitet,Theranostics
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- Andersson, Ken G. (author)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, Stockholm, Sweden
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- Leitao, Charles Dahlsson (author)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, Stockholm, Sweden
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- Frejd, Fredrik Y. (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Löfblom, John (author)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, Stockholm, Sweden
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- Bussink, Johan (author)
- Radboud Univ Nijmegen, Dept Radiat Oncol, Med Ctr, Nijmegen, Netherlands.
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- Orlova, Anna (author)
- Uppsala universitet,Theranostics
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- Heskamp, Sandra (author)
- Radboud Univ Nijmegen, Dept Radiol & Nucl Med, Med Ctr, Nijmegen, Netherlands.
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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(creator_code:org_t)
- 2019-10-17
- 2019
- English.
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Abstract
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- Carbonic anhydrase IX (CAIX) is a cancer-associated molecular target for several classes of therapeutics. CAIX is overexpressed in a large fraction of renal cell carcinomas (RCC). Radionuclide molecular imaging of CAIX-expression might offer a non-invasive methodology for stratification of patients with disseminated RCC for CAIX-targeting therapeutics. Radiolabeled monoclonal antibodies and their fragments are actively investigated for imaging of CAIX expression. Promising alternatives are small non-immunoglobulin scaffold proteins, such as affibody molecules. A CAIX-targeting affibody ZCAIX:2 was re-designed with the aim to decrease off-target interactions and increase imaging contrast. The new tracer, DOTA-HE3-ZCAIX:2, was labeled with In-111 and characterized in vitro. Tumor-targeting properties of [In-111]In-DOTA-HE3-ZCAIX:2 were compared head-to-head with properties of the parental variant, [(99)mTc]Tc(CO)(3)-HE3-ZCAIX:2, and the most promising antibody fragment-based tracer, [In-111]In-DTPA-G250(Fab')(2), in the same batch of nude mice bearing CAIX-expressing RCC xenografts. Compared to the (99)mTc-labeled parental variant, [In-111]In-DOTA-HE3-ZCAIX:2 provides significantly higher tumor-to-lung, tumor-to-bone and tumor-to-liver ratios, which is essential for imaging of CAIX expression in the major metastatic sites of RCC. [In-111]In-DOTA-HE3-ZCAIX:2 offers significantly higher tumor-to-organ ratios compared with [In-111]In-G250(Fab']2. In conclusion, [In-111]In-DOTA-HE3-ZCAIX:2 can be considered as a highly promising tracer for imaging of CAIX expression in RCC metastases based on our results and literature data.
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)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Garousi, Javad
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Huizing, Fokko J ...
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Vorobyeva, Anzhe ...
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Mitran, Bogdan
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Andersson, Ken G ...
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Leitao, Charles ...
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Frejd, Fredrik Y ...
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Löfblom, John
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Bussink, Johan
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Orlova, Anna
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Heskamp, Sandra
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Tolmachev, Vladi ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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Scientific Repor ...
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Royal Institute of Technology
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Uppsala University