uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Identification of positron emission tomography (PET) tracer candidates by prediction of the target-bound fraction in the brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Show others and affiliations
2014 (English)In: EJNMMI Research, ISSN 2191-219X, Vol. 4, 1-8 p., 50Article in journal (Refereed) Published
Abstract [en]

Background: Development of tracers for imaging with positron emission tomography (PET) is often a time-consuming process associated with considerable attrition. In an effort to simplify this process, we herein propose a mechanistically integrated approach for the selection of tracer candidates based on in vitro measurements of ligand affinity (K-d), non-specific binding in brain tissue (V-u,V-brain), and target protein expression (B-max). Methods: A dataset of 35 functional and 12 non-functional central nervous system (CNS) PET tracers was compiled. Data was identified in literature for K-d and B-max, whereas a brain slice methodology was used to determine values for V-u,V-brain. A mathematical prediction model for the target-bound fraction of tracer in the brain (f(tb)) was derived and evaluated with respect to how well it predicts tracer functionality compared to traditional PET tracer candidate selection criteria. Results: The methodology correctly classified 31/35 functioning and 12/12 non-functioning tracers. This predictivity was superior to traditional classification criteria or combinations thereof. Conclusions: The presented CNS PET tracer identification approach is rapid and accurate and is expected to facilitate the development of novel PET tracers for the molecular imaging community.

Place, publisher, year, edition, pages
2014. Vol. 4, 1-8 p., 50
Keyword [en]
Positron emission tomography, Non-specific binding, Imaging, Receptor occupancy
National Category
Radiology, Nuclear Medicine and Medical Imaging
URN: urn:nbn:se:uu:diva-260170DOI: 10.1186/s13550-014-0050-6ISI: 000358050900001PubMedID: 26116114OAI: oai:DiVA.org:uu-260170DiVA: diva2:846522
Available from: 2015-08-17 Created: 2015-08-17 Last updated: 2015-08-17Bibliographically approved

Open Access in DiVA

fulltext(861 kB)43 downloads
File information
File name FULLTEXT01.pdfFile size 861 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Fridén, Markus
By organisation
Department of Pharmaceutical Biosciences
In the same journal
EJNMMI Research
Radiology, Nuclear Medicine and Medical Imaging

Search outside of DiVA

GoogleGoogle Scholar
Total: 43 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 169 hits
ReferencesLink to record
Permanent link

Direct link