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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03788naa a2200409 4500 | |
| 001 | oai:DiVA.org:uu-128315 | |
| 003 | SwePub | |
| 008 | 100720s2009 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1283152 URI |
| 024 | 7 | a https://doi.org/10.1007/s00259-009-1134-92 DOI |
| 040 | a (SwePub)uu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Tolmachev, Vladimiru Uppsala universitet,Institutionen för medicinska vetenskaper4 aut0 (Swepub:uu)vladtolm |
| 245 | 1 0 | a The influence of Bz-DOTA and CHX-AaEuro(3)-DTPA on the biodistribution of ABD-fused anti-HER2 Affibody molecules :b implications for In-114m-mediated targeting therapy |
| 264 | c 2009-05-09 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2009 |
| 338 | a print2 rdacarrier | |
| 520 | a 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. | |
| 653 | a Affibody molecule | |
| 653 | a In-114m | |
| 653 | a Biodistribution | |
| 653 | a Radionuclide therapy | |
| 653 | a Albumin-binding domain | |
| 653 | a MEDICINE | |
| 653 | a MEDICIN | |
| 700 | 1 | a Wallberg, Helena4 aut |
| 700 | 1 | a Andersson, Karlu Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap4 aut |
| 700 | 1 | a Wennborg, Anders4 aut |
| 700 | 1 | a Lundqvist, Hansu Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap4 aut0 (Swepub:uu)hanslund |
| 700 | 1 | a Orlova, Annau Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap4 aut0 (Swepub:uu)annaorlo |
| 710 | 2 | a Uppsala universitetb Institutionen för medicinska vetenskaper4 org |
| 773 | 0 | t European Journal of Nuclear Medicine and Molecular Imagingd : Springer Science and Business Media LLCg 36:9, s. 1460-1468q 36:9<1460-1468x 1619-7070x 1619-7089 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-128315 |
| 856 | 4 8 | u https://doi.org/10.1007/s00259-009-1134-9 |
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