[18F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging

Author:

Knyzeliene Agne12,MacAskill Mark G12,Alcaide-Corral Carlos J12,Morgan Timaeus EF12,Henry Martyn C3,Lucatelli Christophe2,Pimlott Sally L4,Sutherland Andrew3,Tavares Adriana AS12ORCID

Affiliation:

1. BHF-University of Edinburgh Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK

2. Edinburgh Imaging, University of Edinburgh, Edinburgh, UK

3. School of Chemistry, University of Glasgow, Glasgow, UK

4. West of Scotland PET Centre, Greater Glasgow and Clyde NHS Trust, Glasgow, UK

Abstract

Neuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [18F]LW223, in mice and specifically assess its volume of non-displaceable binding ( VND) in brain as well as investigate the use of simplified analysis approaches for quantification of [18F]LW223 PET data. Adult male mice were injected with [18F]LW223 and varying concentrations of LW223 (0.003–0.55 mg/kg) to estimate VND of [18F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values ( SUV) and apparent volume of distribution ( VTapp), were investigated. [18F]LW223 had low VND in the brain (<10% of total binding) and low radiometabolism (∼15–20%). The 2-tissue compartment model provided the best fit for [18F]LW223 PET data, although its correlation with SUV90–120min or VTapp allowed for [18F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [18F]LW223 has the required properties to become a successful TSPO PET radiotracer.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine,Neurology (clinical),Neurology

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