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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},
}