id:"swepub:oai:DiVA.org:uu-488406"
Sökning: id:"swepub:oai:DiVA.org:uu-488406" > Age, dose, and bind...
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04507naa a2200409 4500 | |
| 001 | oai:DiVA.org:uu-488406 | |
| 003 | SwePub | |
| 008 | 230113s2023 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4884062 URI |
| 024 | 7 | a https://doi.org/10.1186/s12987-023-00435-22 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 Faresjö, Rebecca,d 1990-u Uppsala universitet,Geriatrik,Molecular Geriatrics4 aut0 (Swepub:uu)rebfa611 |
| 245 | 1 0 | a Age, dose, and binding to TfR on blood cells influence brain delivery of a TfR-transported antibody |
| 264 | 1 | b BioMed Central (BMC),c 2023 |
| 338 | a electronic2 rdacarrier | |
| 520 | a BackgroundTransferrin receptor 1 (TfR1) mediated brain delivery of antibodies could become important for increasing the efficacy of emerging immunotherapies in Alzheimer's disease (AD). However, age, dose, binding to TfR1 on blood cells, and pathology could influence the TfR1-mediated transcytosis of TfR1-binders across the blood–brain barrier (BBB). The aim of the study was, therefore, to investigate the impact of these factors on the brain delivery of a bispecific TfR1-transported Aβ-antibody, mAb3D6-scFv8D3, in comparison with the conventional antibody mAb3D6.MethodsYoung (3–5 months) and aged (17–20 months) WT and tg-ArcSwe mice (AD model) were injected with 125I-labeled mAb3D6-scFv8D3 or mAb3D6. Three different doses were used in the study, 0.05 mg/kg (low dose), 1 mg/kg (high dose), and 10 mg/kg (therapeutic dose), with equimolar doses for mAb3D6. The dose-corrected antibody concentrations in whole blood, blood cells, plasma, spleen, and brain were evaluated at 2 h post-administration. Furthermore, isolated brains were studied by autoradiography, nuclear track emulsion, and capillary depletion to investigate the intrabrain distribution of the antibodies, while binding to blood cells was studied in vitro using blood isolated from young and aged mice.ResultsThe aged WT and tg-ArcSwe mice showed significantly lower brain concentrations of TfR-binding [125I]mAb3D6-scFv8D3 and higher concentrations in the blood cell fraction compared to young mice. For [125I]mAb3D6, no significant differences in blood or brain delivery were observed between young and aged mice or between genotypes. A low dose of [125I]mAb3D6-scFv8D3 was associated with increased relative parenchymal delivery, as well as increased blood cell distribution. Brain concentrations and relative parenchymal distribution of [125I]mAb3D6-scFv8D6 did not differ between tg-ArcSwe and WT mice at this early time point but were considerably increased compared to those observed for [125I]mAb3D6.ConclusionAge-dependent differences in blood and brain concentrations were observed for the bispecific antibody mAb3D6-scFv8D3 but not for the conventional Aβ antibody mAb3D6, indicating an age-related effect on TfR1-mediated brain delivery. The lowest dose of [125I]mAb3D6-scFv8D3 was associated with higher relative BBB penetration but, at the same time, a higher distribution to blood cells. Overall, Aβ-pathology did not influence the early brain distribution of the bispecific antibody. In summary, age and bispecific antibody dose were important factors determining brain delivery, while genotype was not. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng |
| 653 | a brain delivery | |
| 653 | a bispecific antibody | |
| 653 | a age | |
| 653 | a aging | |
| 653 | a transferrin receptor | |
| 653 | a Biopharmaceutics | |
| 653 | a Biofarmaci | |
| 700 | 1 | a Sehlin, Dag,d 1976-u Uppsala universitet,Geriatrik,Molecular Geriatrics4 aut0 (Swepub:uu)daseh499 |
| 700 | 1 | a Syvänen, Stinau Uppsala universitet,Geriatrik,Molecular Geriatrics4 aut0 (Swepub:uu)stsyv838 |
| 710 | 2 | a Uppsala universitetb Geriatrik4 org |
| 773 | 0 | t Fluids and Barriers of the CNSd : BioMed Central (BMC)g 20:1q 20:1x 2045-8118 |
| 856 | 4 | u https://doi.org/10.1186/s12987-023-00435-2y Fulltext |
| 856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1726957/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-488406 |
| 856 | 4 8 | u https://doi.org/10.1186/s12987-023-00435-2 |
Hitta via bibliotek
- Fluids and Barriers of the CNS (Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
Hitta mer i SwePub
- Av författaren/redakt...
- Faresjö, Rebecca ...
- Sehlin, Dag, 197 ...
- Syvänen, Stina
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
- MEDICIN OCH HÄLS ...
- och Medicinska och f ...
- och Neurovetenskaper
- Artiklar i publikationen
- Fluids and Barri ...
- Av lärosätet
- Uppsala universitet
Sök utanför SwePub
- Sök vidare i:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - Nationella bibliotekssystem
- LIBRIS.kb.se
