WFRF:(Wennborg Anders)
Sökning: WFRF:(Wennborg Anders) > (2005-2009) > The influence of Bz...
The influence of Bz-DOTA and CHX-AaEuro(3)-DTPA on the biodistribution of ABD-fused anti-HER2 Affibody molecules : implications for In-114m-mediated targeting therapy
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper
- Wallberg, Helena (författare)
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- Andersson, Karl (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Wennborg, Anders (författare)
- visa färre...
- (creator_code:org_t)
- 2009-05-09
- 2009
- Engelska.
- Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 36:9, s. 1460-1468
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Affibody molecules represent a novel class of high-affinity agents for radionuclide tumour targeting. Fusion of the Affibody molecules with an albumin-binding domain (ABD) enables modification of the blood kinetics of the Affibody molecules and reduction of the renal dose. Lu-177-CHX-AaEuro(3)-DTPA-ABD-(Z(HER2:342))(2), an anti-HER2 Affibody molecule-ABD fusion protein has earlier demonstrated promising results in treatment of HER2-expressing micro-xenografts in mice. The use of the in vivo generator In-114m/In-114 as a label for ABD-fused Affibody molecules would create preconditions for efficient treatment of both micrometastases (due to conversion and Auger electrons of In-114m) and bulky tumours (due to high-energy beta particles from the daughter nuclide In-114). The goal of this study was to investigate if different chelators influence the biodistribution of ABD-(Z(HER2:342))(2) and to find an optimal chelator for attachment of In-114m to the Affibody molecule-ABD fusion protein. Isothiocyanate derivatives of Bz-DOTA and CHX-AaEuro(3)-DTPA were coupled to ABD-(Z(HER2:342))(2). The cellular processing of both conjugates was studied in vitro. The influence of chelators on the biodistribution was investigated in mice using double isotope (In-114m and In-111) labelling. The apparent affinity of CHX-AaEuro(3)-DTPA-ABD-(Z(HER2:342))(2) and Bz-DOTA-ABD-(Z(HER2:342))(2) to the extracellular domain of HER2 was similar, 13.5 and 15.0 pM, respectively. It was found that both conjugates were internalized by SKOV-3 cells. The use of CHX-AaEuro(3)-DTPA provided better cellular retention of the radioactivity, better tumour accumulation of radioactivity and better tumour to organ dose ratios than Bz-DOTA-ABD-(Z(HER2:342))(2). CHX-AaEuro(3)-DTPA is more suitable for In-114m labelling of Affibody molecule-ABD fusion proteins for radionuclide therapy.
Nyckelord
- Affibody molecule
- In-114m
- Biodistribution
- Radionuclide therapy
- Albumin-binding domain
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- European Journal of Nuclear Medicine and Molecular Imaging (Sök värdpublikationen i LIBRIS)
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- Tolmachev, Vladi ...
- Wallberg, Helena
- Andersson, Karl
- Wennborg, Anders
- Lundqvist, Hans
- Orlova, Anna
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- Uppsala universitet
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