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> Varasteh Zohreh >
Direct comparison o...
Direct comparison of In-111-labelled two-helix and three-helix Affibody molecules for in vivo molecular imaging
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- Rosik, Daniel (författare)
- KTH,Molekylär Bioteknologi
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- Orlova, Anna (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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- Malmberg, Jennie (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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- Altai, Mohamed (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Varasteh, Zohreh (författare)
- Uppsala universitet,Plattformen för preklinisk PET
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- Sandström, Mattias (författare)
- Uppsala universitet,Avdelningen för sjukhusfysik
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- Eriksson Karlström, Amelie (författare)
- KTH,Molekylär Bioteknologi
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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(creator_code:org_t)
- 2011-12-15
- 2012
- Engelska.
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:4, s. 693-702
- 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
- Radiolabelled Affibody molecules have demonstrated a potential for visualization of tumour-associated molecular targets. Affibody molecules (7 kDa) are composed of three alpha-helices. Recently, a smaller two-helix variant of Affibody molecules (5.1 kDa) was developed. The aim of this study was to compare two- and three-helix HER2-targeting Affibody molecules directly in vivo. The three-helix Affibody molecule ABY-002 and the two-helix Affibody molecule PEP09239 were labelled with In-111 at the N-termini via DOTA chelator. Tumour-targeting properties were directly compared at 1 and 4 h after injection in mice bearing SKOV-3 xenografts with high HER2 expression and LS174T xenografts with low HER2 expression. The dissociation constants (K (D)) for HER2 binding were 78 pM for the three-helix Affibody molecule and 2.1 nM for the two-helix Affibody molecule. In-111-PEP09239 cleared more rapidly from the blood. In xenografts with high HER2 expression, the uptake of In-111-ABY-002 was significantly higher than that of In-111-PEP09239. The tumour-to-blood ratio was higher for In-111-PEP09239 at 4 h after injection, while there was no significant difference in other tumour-to-organ ratios. The tumour uptake of In-111-ABY-002 was eightfold higher than that of In-111-PEP09239 in xenografts with low expression. Tumour-to-blood ratios were equal in this case, but other tumour-to-organ ratios were appreciably higher for the three-helix variant. For tumours with high HER2 expression, two-helix HER2-targeting Affibody molecules can provide higher tumour-to-blood ratio at the cost of lower tumour uptake. In the case of low expression, both tumour uptake and tumour-to-organ ratios are appreciably higher for three-helix than for two-helix HER2-targeting Affibody molecules.
Ämnesord
- TEKNIK OCH TEKNOLOGIER -- Medicinteknik -- Medicinsk laboratorie- och mätteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Medical Engineering -- Medical Laboratory and Measurements Technologies (hsv//eng)
Nyckelord
- 111In-ABY-002
- 111In-PEP09239
- Affibody
- HER2 targeting
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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