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Radiosynthesis and in Vivo Evaluation of [11C]A1070722, a High Affinity GSK-3 PET Tracer in Primate Brain
- Publication Year :
- 2017
-
Abstract
- Dysfunction of glycogen synthase kinase 3 (GSK-3) is implicated in the etiology of Alzheimer’s disease, Parkinson’s disease, diabetes, pain, and cancer. A radiotracer for functional positron emission tomography (PET) imaging could be used to study the kinase in brain disorders and to facilitate the development of small molecule inhibitors of GSK-3 for treatment. At present, there is no target-specific or validated PET tracer available for the in vivo monitoring of GSK-3. We radiolabeled the small molecule inhibitor [11C]1-(7-methoxy-quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)urea ([11C]A1070722) with high affinity to GSK-3 (Ki = 0.6 nM) in excellent radiochemical yield. PET imaging experiments in anesthetized vervet/African green monkey exhibited that [11C]A1070722 penetrated the blood-brain barrier (BBB) and accumulated in brain regions, with highest radioactivity binding in frontal cortex followed by parietal cortex and anterior cingulate, and with the lowest bindings found in caudate, putamen, and thalamus, similarly to the known distribution of GSK-3 in human brain. Our studies suggest that [11C]A1070722 can be a potential PET radiotracer for the in vivo quantification of GSK-3 in brain.
- Subjects :
- 0301 basic medicine
Male
Pathology
medicine.medical_specialty
Physiology
Cognitive Neuroscience
Drug Evaluation, Preclinical
Pharmacology
Biochemistry
Brain mapping
Article
Capillary Permeability
03 medical and health sciences
Glycogen Synthase Kinase 3
0302 clinical medicine
In vivo
GSK-3
Chlorocebus aethiops
medicine
Animals
Urea
Brain Mapping
medicine.diagnostic_test
Chemistry
Kinase
Putamen
Radiosynthesis
Brain
Cell Biology
General Medicine
Small molecule
Magnetic Resonance Imaging
030104 developmental biology
Positron emission tomography
Positron-Emission Tomography
Quinolines
Radiopharmaceuticals
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....91be889b10ce29088b1a3e68bedebcb4