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  • Sehlin, Dag,1976-Uppsala universitet,Geriatrik (author)

Engineered antibodies : new possibilities for brain PET?

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-07-24
  • SPRINGER,2019
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-401995
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-401995URI
  • https://doi.org/10.1007/s00259-019-04426-0DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:142513156URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:for swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Syvänen, StinaUppsala universitet,Geriatrik(Swepub:uu)stsyv838 (author)
  • Ballanger, BenedicteLyon Neurosci Res Ctr, Lyon, France (author)
  • Barthel, Henryk (author)
  • Bischof, Gerard N.Univ Cologne, Univ Hosp Cologne, Cologne, Germany (author)
  • Boche, DelphineUniv Southampton, Southampton, Hants, England (author)
  • Boecker, HennigUniv Leipzig, Univ Hosp Leipzig, Leipzig, Germany;German Ctr Neurodegenerat Dis DZNE, Bonn, Germany (author)
  • Bohn, Karl PeterUniv Cologne, Univ Hosp Cologne, Cologne, Germany (author)
  • Borghammer, PerAarhus Univ, Aarhus, Denmark (author)
  • Cross, DonnaUniv Utah, Salt Lake City, UT 84112 USA (author)
  • Di Monte, DonatoGerman Ctr Neurodegenerat Dis DZNE, Bonn, Germany (author)
  • Drzezga, AlexanderUniv Cologne, Univ Hosp Cologne, Cologne, Germany;Res Ctr Julich, Julich, Germany (author)
  • Endepols, HeikeUniv Cologne, Univ Hosp Cologne, Cologne, Germany (author)
  • Giehl, KathrinUniv Cologne, Univ Hosp Cologne, Cologne, Germany (author)
  • Goedert, MichelMRC, Mol Biol Lab, Cambridge, England (author)
  • Hammes, JochenUniv Cologne, Univ Hosp Cologne, Cologne, Germany (author)
  • Hansson, OskarLund Univ, Lund, Sweden (author)
  • Herholz, KarlUniv Manchester, Manchester, Lancs, England (author)
  • Hoeglinger, GuenterGerman Ctr Neurodegenerat Dis DZNE, Munich, Germany (author)
  • Hoenig, MerleUniv Cologne, Univ Hosp Cologne, Cologne, Germany (author)
  • Jessen, FrankUniv Cologne, Univ Hosp Cologne, Cologne, Germany (author)
  • Klockgether, ThomasGerman Ctr Neurodegenerat Dis DZNE, Bonn, Germany (author)
  • Lafaye, PierreInst Pasteur, Paris, France (author)
  • Lammerstma, AdriaanUniv Amsterdam, Med Ctr, Amsterdam, Netherlands (author)
  • Mandelkow, Eckhard (author)
  • Mandelkow, Eva-Maria (author)
  • Maurer, AndreasUniv Tubingen Hosp, Tubingen, Germany (author)
  • Mollenhauer, BritUniv Med Ctr Gottingen, Gottingen, Germany (author)
  • Neumaier, BerndRes Ctr Julich, Julich, Germany (author)
  • Nordberg, AgnetaKarolinska Institutet (author)
  • Onur, Ozgur (author)
  • Reetz, KathrinUniv Hosp Aachen, Aachen, Germany (author)
  • Rodriguez-Vietez, ElenaKarolinska Inst, Stockholm, Sweden (author)
  • Rominger, AxelUniv Bern, Bern, Switzerland (author)
  • Rowe, JamesUniv Cambridge, Cambridge, England;MRC, Cognit & Brain Sci Unit, Cambridge, England (author)
  • Sabri, OsamaUniv Leipzig, Univ Hosp Leipzig, Leipzig, Germany (author)
  • Schneider, Anja (author)
  • Strafella, AntonioUniv Toronto, Toronto, ON, Canada;Toronto Western Hosp, UHN, Toronto, ON, Canada (author)
  • van Eimeren, Thilo (author)
  • Vasdev, NeilCtr Addict & Mental Hlth CAMH, Toronto, ON, Canada (author)
  • Villemagne, VictorAustin Hlth, Heidelberg, Vic, Australia (author)
  • Willbold, DieterRes Ctr Julich, Julich, Germany (author)
  • Uppsala universitetGeriatrik (creator_code:org_t)

Related titles

  • In:European Journal of Nuclear Medicine and Molecular Imaging: SPRINGER46:13, s. 2848-28581619-70701619-7089

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