Sehlin, Dag, Syvanen, Stina ORCID: 0000-0002-8196-4041, Ballanger, Benedicte ORCID: 0000-0002-1901-3501, Barthel, Henryk, Bischof, Gerard N., Boche, Delphine ORCID: 0000-0002-5884-130X, Boecker, Hennig, Bohn, Karl Peter, Borghammer, Per ORCID: 0000-0001-6391-8052, Cross, Donna, Di Monte, Donato, Drzezga, Alexander, Endepols, Heike ORCID: 0000-0002-6166-4818, Giehl, Kathrin, Goedert, Michel, Hammes, Jochen, Hansson, Oskar ORCID: 0000-0001-8467-7286, Herholz, Karl, Hoeglinger, Guenter, Hoenig, Merle, Jessen, Frank, Klockgether, Thomas, Lafaye, Pierre, Lammerstma, Adriaan, Mandelkow, Eckhard, Mandelkow, Eva-Maria, Maurer, Andreas, Mollenhauer, Brit, Neumaier, Bernd, Nordberg, Agneta, Onur, Ozgur, Reetz, Kathrin, Rodriguez-Vietez, Elena, Rominger, Axel, Rowe, James ORCID: 0000-0001-7216-8679, Sabri, Osama, Schneider, Anja, Strafella, Antonio, Syvanen, Stina ORCID: 0000-0002-8196-4041, van Eimeren, Thilo, Vasdev, Neil, Villemagne, Victor and Willbold, Dieter (2019). Engineered antibodies: new possibilities for brain PET? Eur. J. Nucl. Med. Mol. Imaging, 46 (13). S. 2848 - 2859. NEW YORK: SPRINGER. ISSN 1619-7089

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sehlin, DagUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Syvanen, StinaUNSPECIFIEDorcid.org/0000-0002-8196-4041UNSPECIFIED
Ballanger, BenedicteUNSPECIFIEDorcid.org/0000-0002-1901-3501UNSPECIFIED
Barthel, HenrykUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bischof, Gerard N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boche, DelphineUNSPECIFIEDorcid.org/0000-0002-5884-130XUNSPECIFIED
Boecker, HennigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bohn, Karl PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borghammer, PerUNSPECIFIEDorcid.org/0000-0001-6391-8052UNSPECIFIED
Cross, DonnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Di Monte, DonatoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drzezga, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Endepols, HeikeUNSPECIFIEDorcid.org/0000-0002-6166-4818UNSPECIFIED
Giehl, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goedert, MichelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hammes, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansson, OskarUNSPECIFIEDorcid.org/0000-0001-8467-7286UNSPECIFIED
Herholz, KarlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoeglinger, GuenterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoenig, MerleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klockgether, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lafaye, PierreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lammerstma, AdriaanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mandelkow, EckhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mandelkow, Eva-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maurer, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mollenhauer, BritUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumaier, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordberg, AgnetaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Onur, OzgurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reetz, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez-Vietez, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rominger, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rowe, JamesUNSPECIFIEDorcid.org/0000-0001-7216-8679UNSPECIFIED
Sabri, OsamaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strafella, AntonioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Syvanen, StinaUNSPECIFIEDorcid.org/0000-0002-8196-4041UNSPECIFIED
van Eimeren, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vasdev, NeilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villemagne, VictorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willbold, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-125854
DOI: 10.1007/s00259-019-04426-0
Journal or Publication Title: Eur. J. Nucl. Med. Mol. Imaging
Volume: 46
Number: 13
Page Range: S. 2848 - 2859
Date: 2019
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1619-7089
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POSITRON-EMISSION-TOMOGRAPHY; AMYLOID-BETA; TRANSFERRIN RECEPTOR; ALZHEIMERS-DISEASE; PROSTHETIC GROUP; MOUSE-BRAIN; IMMUNO-PET; BARRIER; DEPOSITION; ASTROCYTOSISMultiple languages
Radiology, Nuclear Medicine & Medical ImagingMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12585

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