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Preclinical evaluat...
Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with In-111 using a maleimido derivative of NODAGA
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- Altai, Mohamed (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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- Perols, Anna (författare)
- KTH,Molekylär Bioteknologi
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- Eriksson Karlström, Amelie (författare)
- KTH,Molekylär Bioteknologi
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- Sandström, Mattias (författare)
- Uppsala universitet,Avdelningen för sjukhusfysik
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Boschetti, Frederic (författare)
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- Orlova, Anna (författare)
- Uppsala universitet,Plattformen för preklinisk PET,Anna Orlova
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev
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(creator_code:org_t)
- Elsevier BV, 2012
- 2012
- Engelska.
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 39:4, s. 518-529
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-l-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule. Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to Z(HER2:2395) Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) were studied. Biodistribution of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) was compared in mice. Results: The affinity of [MMA-NODAGA-Cys(61)]-Z(HER2:2395) binding to HER2 was 67 pM. The In-1111-labeling yield was 99.6%+/- 0.5% after 30 min at 60 degrees C. [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [In-111-MMA-NODAGA-Cys(61)]-ZHER(2:2395) in mice bearing DU-145 xenografts (4.7%+/- 0.8% ID/g) was lower than uptake of [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) (7.5%+/- 1.6% ID/g). However, tumor-to-organ ratios were higher for [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) due to higher clearance rate from normal tissues. Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Nyckelord
- HER2
- Affibody molecules
- Radionuclides
- Receptor targeting
- Molecular imaging
- Indium-111
- Maleimido-NODAGA
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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