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Cationization incre...
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Syvänen, StinaUppsala universitet,Geriatrik
(författare)
Cationization increases brain distribution of an amyloid-beta protofibril selective F(ab')2 fragment
- Artikel/kapitelEngelska2017
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Elsevier BV,2017
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LIBRIS-ID:oai:DiVA.org:uu-339734
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-339734URI
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https://doi.org/10.1016/j.bbrc.2017.09.065DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Antibodies and fragments thereof are, because of high selectivity for their targets, considered as potential therapeutics and biomarkers for several neurological disorders. However, due to their large molecular size, antibodies/fragments do not easily penetrate into the brain. The aim of the present study was to improve the brain distribution via adsorptive-mediated transcytosis of an amyloid-beta (A beta) protofibril selective F(ab')2 fragment (F(ab')2-h158). F(ab')2-h158 was cationized to different extents and the specific and unspecific binding was studied in vitro. Next, cationized F(ab')2-h158 was labelled with iodine-125 and its brain distribution and pharmacokinetics was studied in mice. Cationization did not alter the in vitro affinity to A beta protofibrils, but increased the unspecific binding somewhat. Ex vivo experiments revealed a doubling of brain concentrations compared with unmodified F(ab')2-h158 and in vivo imaging with single photon emission computed tomography (SPECT) showed that the cationized F(ab')2-h158, but not the unmodified F(ab')2-h158 could be visualized in the brain. To conclude, cationization is a means to increase brain concentrations of therapeutic antibodies or fragments and may facilitate the use of antibodies/fragments as imaging biomarkers in the brain.
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Edén, DesireéUppsala universitet,Klinisk kemi(Swepub:uu)desed692
(författare)
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Sehlin, Dag,1976-Uppsala universitet,Geriatrik(Swepub:uu)daseh499
(författare)
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Uppsala universitetGeriatrik
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Biochemical and Biophysical Research Communications - BBRC: Elsevier BV493:1, s. 120-1250006-291X1090-2104
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