title: PET imaging of demyelination and remyelination in the cuprizone mouse model for multiple sclerosis: a comparison between [11C]CIC and [11C]MeDAS.
abstract: Multiple Sclerosis (MS) is a neurodegenerative disease characterized by demyelinated lesions. PET imaging using specific myelin radioligands might solve the lack of a specific imaging tool for diagnosing and monitoring demyelination and remyelination in MS patients. In recent years, a few tracers have been developed for in vivo PET imaging of myelin, but they have not been fully evaluated yet. In this study, we compared [(11)C]CIC and [(11)C]MeDAS as PET tracers for monitoring demyelination and remyelination in cuprizone-fed mice. The ex vivo biodistribution of [(11)C]CIC showed decreased tracer uptake in mice fed with 0.2% cuprizone diet for 5 weeks, as compared to control mice. However, tracer uptake did not increase again after normal diet was restored for 5 weeks (remyelination). Surprisingly, in vivo PET imaging with [(11)C]CIC in cuprizone-fed mice revealed a significant reduction in whole brain tracer uptake after 5 weeks of remyelination. No correlation between ex vivo biodistribution and in vivo imaging data was found for [(11)C]CIC (r(2)=0.15, p=0.11). However, a strong correlation was found for [(11)C]MeDAS (r(2)=0.88, p<0.0001). [(11)C]MeDAS ex vivo biodistribution revealed significant decreased brain uptake in the demyelination group, as compared to controls and increased the tracer uptake after 5 weeks of remyelination. [(11)C]MeDAS images showed a low background signal and clear uptake in the brain white matter and spinal cord. Taken together, the results of this comparative study between [(11)C]CIC and [(11)C]MeDAS clearly show that [(11)C]MeDAS is the preferred PET tracer to monitor myelin changes in the brain and spinal cord in vivo.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, The Netherlands; Department of Neuroscience, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, The Netherlands; Center of Nuclear Medicine, University of Sao Paulo, University of Sao Paulo Medical School, Sao Paulo 05403-900, Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: de Paula Faria
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, The Netherlands. Electronic address: e.f.j.de.vries@umcg.nl.
authors.forename: Erik F J
authors.initials: EF
authors.lastname: de Vries
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, The Netherlands.
authors.forename: Jurgen W A
authors.initials: JW
authors.lastname: Sijbesma
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, The Netherlands.
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: Center of Nuclear Medicine, University of Sao Paulo, University of Sao Paulo Medical School, Sao Paulo 05403-900, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Buchpiguel
authors.affiliation: Department of Neuroscience, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, The Netherlands.
authors.forename: Sjef
authors.initials: S
authors.lastname: Copray
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000494:pharmacology*; D002614:Chelating Agents / Q000633:toxicity; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000000981:diagnostic imaging*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology*
chemical_list: D002250:Carbon Radioisotopes; D002614:Chelating Agents; D019275:Radiopharmaceuticals; D003471:Cuprizone
keywords: Cuprizone model; Demyelination; MRI; MS; Magnetic Resonance Imaging; Multiple Sclerosis; Myelin; PET; PET imaging; Positron Emission Tomography; Remyelination; SUV; Standardized Uptake Value