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Evaluation of a Mal...
Evaluation of a Maleimido Derivative of NOTA for Site-Specific Labeling of Affibody Molecules
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Altai, Mohamed (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Sandström, Mattias (author)
- Uppsala universitet,Enheten för onkologi
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- Perols, Anna (author)
- KTH,Molekylär Bioteknologi
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- Eriksson Karlström, Amelie (author)
- KTH,Molekylär Bioteknologi
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Boschetti, Frederic (author)
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- Orlova, Anna (author)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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(creator_code:org_t)
- 2011-04-12
- 2011
- English.
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In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 22:5, s. 894-902
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Radionuclide molecular imaging has the potential to improve cancer treatment by selection of patients for targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. The NOTA chelator forms stable complexes with a number of radionuclides suitable for SPECT or PET imaging. A maleimidoethylmonoamide NOTA (MMA-NOTA) has been prepared for site-specific labeling of Affibody molecules having a unique C-terminal cysteine. Coupling of the MMA-NOTA to the anti-HER2 Affibody molecule Z(HER2:239S) resulted in a conjugate with an affinity (dissociation constant) to HER2 of 72 pM. Labeling of [MMA-NOTA-Cys(61)]-Z(HER2:239S) with In-111 gave a yield of >95% after 20 min at 60 degrees C. In vitro cell tests demonstrated specific binding of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) to HER2-expressing cell lines. In mice bearing prostate cancer DU-145 xenografts, the tumor uptake of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) was 8.2 +/- 0.9% IA/g and the tumor-to-blood ratio was 31 +/- 1 (4 h postinjection). DU-145 xenografts were clearly visualized by a gamma camera. Direct in vivo comparison of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:239S) demonstrated that both conjugates provided equal radioactivity uptake in tumors, but the tumor-to-organ ratios were better for [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) due to more efficient clearance from normal tissues. In conclusion, coupling of MMA-NOTA to a cysteine-containing Affibody molecule resulted in a site-specifically labeled conjugate, which retains high affinity, can be efficiently labeled, and allows for high-contrast imaging.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Keyword
- Biochemistry
- Biokemi
- Molecular biology
- Molekylärbiologi
- Organic chemistry
- Organisk kemi
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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