Loading...
Please wait, while we are loading the content...
Similar Documents
Fluorine-18-Labeled Antibody Ligands for PET Imaging of Amyloid-β in Brain.
| Content Provider | Europe PMC |
|---|---|
| Author | Syvänen, Stina Fang, Xiaotian T Faresjö, Rebecca Rokka, Johanna Lannfelt, Lars Olberg, Dag E Eriksson, Jonas Sehlin, Dag |
| Copyright Year | 2020 |
| Abstract | Antibodiesare attractive as radioligands due to their outstandingspecificity and high affinity, but their inability to cross the blood–brainbarrier (BBB) limits their use for CNS targets. To enhance brain distribution,amyloid-β (Aβ) antibodies were fused to a transferrinreceptor (TfR) antibody fragment, enabling receptor mediated transportacross the BBB. The aim of this study was to label these bispecificantibodies with fluorine-18 and use them for Aβ PET imaging.Bispecific antibody ligands RmAb158-scFv8D3 and Tribody A2, both targetingAβ and TfR, were functionalized with trans-cyclooctene(TCO) groups and conjugated with 18F-labeled tetrazinesthrough an inverse electron demand Diels–Alder reaction performedat ambient temperature. 18F-labeling did not affect antibodybinding in vitro, and initial brain uptake was high.Conjugates with the first tetrazine variant ([18F]T1) displayedhigh uptake in bone, indicating extensive defluorination, a problemthat was resolved with the second and third tetrazine variants ([18F]T2 and [18F]T3). Although the antibody ligands’half-life in blood was too long to optimally match the physical half-lifeof fluorine-18 (t1/2 = 110 min), [18F]T3-Tribody A2 PET seemed to discriminate transgenic mice(tg-ArcSwe) with Aβ deposits from wild-type mice 12 h afterinjection. This study demonstrates that 18F-labeling ofbispecific, brain penetrating antibodies is feasible and, with furtheroptimization, could be used for CNS PET imaging. |
| Related Links | https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7747219&blobtype=pdf |
| Journal | ACS Chemical Neuroscience [ACS Chem Neurosci] |
| Volume Number | 11 |
| DOI | 10.1021/acschemneuro.0c00652 |
| PubMed Central reference number | PMC7747219 |
| Issue Number | 24 |
| PubMed reference number | 33236886 |
| e-ISSN | 19487193 |
| Language | English |
| Publisher | American ChemicalSociety |
| Publisher Date | 2020-11-25 |
| Access Restriction | Open |
| Rights License | This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. © 2020 AmericanChemical Society |
| Subject Keyword | Fluorine-18 antibody radioligand positronemission tomography (PET) inverse electron demand Diels−Alderreaction tetrazine trans-cyclooctene(TCO) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry Cell Biology Physiology Medicine Cognitive Neuroscience |
