[ 18 F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging.
Agne KnyzelieneMark G MacAskillCarlos J Alcaide-CorralTimaeus Ef MorganMartyn C HenryChristophe LucatelliSally L PimlottAndrew SutherlandAdriana A S TavaresPublished in: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2023)
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, [ 18 F]LW223, in mice and specifically assess its volume of non-displaceable binding ( V ND ) in brain as well as investigate the use of simplified analysis approaches for quantification of [ 18 F]LW223 PET data. Adult male mice were injected with [ 18 F]LW223 and varying concentrations of LW223 (0.003-0.55 mg/kg) to estimate V ND of [ 18 F]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 ( V Tapp ), were investigated. [ 18 F]LW223 had low V ND in the brain (<10% of total binding) and low radiometabolism (∼15-20%). The 2-tissue compartment model provided the best fit for [ 18 F]LW223 PET data, although its correlation with SUV 90-120min or V Tapp allowed for [ 18 F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [ 18 F]LW223 has the required properties to become a successful TSPO PET radiotracer.
Keyphrases
- pet imaging
- positron emission tomography
- computed tomography
- cerebral ischemia
- white matter
- resting state
- pet ct
- electronic health record
- traumatic brain injury
- subarachnoid hemorrhage
- machine learning
- multiple sclerosis
- magnetic resonance imaging
- dna binding
- metabolic syndrome
- mass spectrometry
- brain injury
- high resolution
- lipopolysaccharide induced
- deep learning
- inflammatory response
- lps induced
- skeletal muscle
- small molecule
- transcription factor
- amino acid
- artificial intelligence