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@ARTICLE{Sehlin:910744,
author = {Sehlin, Dag and Syvänen, Stina and Drzezga, Alexander and
faculty, MINC},
title = {{E}ngineered antibodies: new possibilities for brain
{PET}?},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {46},
number = {13},
issn = {0340-6997},
address = {Heidelberg [u.a.]},
publisher = {Springer-Verl.},
reportid = {FZJ-2022-04114},
pages = {2848 - 2858},
year = {2019},
abstract = {Almost 50 million people worldwide are affected by
Alzheimer's disease (AD), the most common neurodegenerative
disorder. Development of disease-modifying therapies would
benefit from reliable, non-invasive positron emission
tomography (PET) biomarkers for early diagnosis, monitoring
of disease progression, and assessment of therapeutic
effects. Traditionally, PET ligands have been based on small
molecules that, with the right properties, can penetrate the
blood-brain barrier (BBB) and visualize targets in the
brain. Recently a new class of PET ligands based on
antibodies have emerged, mainly in applications related to
cancer. While antibodies have advantages such as high
specificity and affinity, their passage across the BBB is
limited. Thus, to be used as brain PET ligands, antibodies
need to be modified for active transport into the brain.
Here, we review the development of radioligands based on
antibodies for visualization of intrabrain targets. We focus
on antibodies modified into a bispecific format, with the
capacity to undergo transferrin receptor 1 (TfR1)-mediated
transcytosis to enter the brain and access pathological
proteins, e.g. amyloid-beta. A number of such antibody
ligands have been developed, displaying differences in brain
uptake, pharmacokinetics, and ability to bind and visualize
the target in the brain of transgenic mice. Potential
pathological changes related to neurodegeneration, e.g.
misfolded proteins and neuroinflammation, are suggested as
future targets for this novel type of radioligand.
Challenges are also discussed, such as the temporal match of
radionuclide half-life with the ligand's pharmacokinetic
profile and translation to human use. In conclusion, brain
PET imaging using bispecific antibodies, modified for
receptor-mediated transcytosis across the BBB, is a
promising method for specifically visualizing molecules in
the brain that are difficult to target with traditional
small molecule ligands.Keywords: Alzheimer’s disease (AD);
Amyloid-β (Aβ); Antibody; Blood–brain barrier (BBB);
Positron emission tomography (PET); Transferrin receptor 1
(TfR1)-mediated transcytosis.},
cin = {INM-2},
ddc = {610},
cid = {I:(DE-Juel1)INM-2-20090406},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {31342134},
UT = {WOS:000502971900023},
doi = {10.1007/s00259-019-04426-0},
url = {https://juser.fz-juelich.de/record/910744},
}