[en] Neurodegenerative diseases such as Parkinson's disease (PD) are manifested by inclusion bodies of alpha-synuclein (α-syn) also called α-synucleinopathies. Detection of these inclusions is thus far only possible by histological examination of postmortem brain tissue. The possibility of non-invasively detecting α-syn will therefore provide valuable insights into the disease progression of α-synucleinopathies. In particular, α-syn imaging can quantify changes in monomeric, oligomeric, and fibrillic α-syn over time and improve early diagnosis of various α-synucleinopathies or monitor treatment progress. Positron emission tomography (PET) is a non-invasive in vivo imaging technique that can quantify target expression and drug occupancies when a suitable tracer exists. As such, novel α-syn PET tracers are highly sought after. The development of an α-syn PET tracer faces several challenges. For example, the low abundance of α-syn within the brain necessitates the development of a high-affinity ligand. Moreover, α-syn depositions are, in contrast to amyloid proteins, predominantly localized intracellularly, limiting their accessibility. Furthermore, another challenge is the ligand selectivity over structurally similar amyloids such as amyloid-beta or tau, which are often co-localized with α-syn pathology. The lack of a defined crystal structure of α-syn has also hindered rational drug and tracer design efforts. Our objective for this review is to provide a comprehensive overview of current efforts in the development of selective α-syn PET tracers.
Precision for document type :
Review article
Disciplines :
Chemistry
Author, co-author :
Korat, Špela; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universeit Amsterdam, De Boelelaan 1085c, 1081 HV Amsterdam, The Netherlands
Bidesi, Natasha Shalina Rajani; Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 160, 2100 Copenhagen, Denmark
Bonanno, Federica; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 15, 72076 Tübingen, Germany
Di Nanni, Adriana; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 15, 72076 Tübingen, Germany
Herfert, Kristina; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 15, 72076 Tübingen, Germany
Maurer, Andreas ; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 15, 72076 Tübingen, Germany
Battisti, Umberto Maria; Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 160, 2100 Copenhagen, Denmark
Bowden, Gregory David ; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Röntgenweg 15, 72076 Tübingen, Germany
Thonon, David ; Université de Liège - ULiège > Unités de recherche interfacultaires > GIGA-CRC In vivo Imaging (Centre de Recherche du Cyclotron)
Vugts, Daniëlle; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universeit Amsterdam, De Boelelaan 1085c, 1081 HV Amsterdam, The Netherlands
Windhorst, Albert Dirk; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universeit Amsterdam, De Boelelaan 1085c, 1081 HV Amsterdam, The Netherlands
Herth, Matthias Manfred; Department of Drug Design and Pharmacology, University of Copenhagen, Jagtvej 160, 2100 Copenhagen, Denmark ; Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark
Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant, agreement no 813528.
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