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A novel PET marker for in vivo quantification of myelination.

ABSTRACT: C-11-labeled N-methyl-4,4'-diaminostilbene ([(11)C]MeDAS) was synthesized and evaluated as a novel radiotracer for in vivo microPET imaging of myelination. [(11)C]MeDAS exhibits optimal lipophilicity for brain uptake with a logP(oct) value of 2.25. Both in vitro and ex vivo staining exhibited MeDAS accumulation in myelinated regions such as corpus callosum and striatum. The corpus callosum region visualized by MeDAS is much larger in the hypermyelinated Plp-Akt-DD mouse brain than in the wild-type mouse brain, a pattern that was also consistently observed in Black-Gold or MBP antibody staining. Ex vivo autoradiography demonstrated that [(11)C]MeDAS readily entered the mouse brain and selectively labeled myelinated regions with high specificity. Biodistribution studies showed abundant initial brain uptake of [(11)C]MeDAS with 2.56% injected dose/whole brain at 5 min post injection and prolonged retention in the brain with 1.37% injected dose/whole brain at 60 min post injection. An in vivo pharmacokinetic profile of [(11)C]MeDAS was quantitatively analyzed through a microPET study in an Plp-Akt-DD hypermyelinated mouse model. MicroPET studies showed that [(11)C]MeDAS exhibited a pharmacokinetic profile that readily correlates the radioactivity concentration to the level of myelination in the brain. These studies suggest that MeDAS is a sensitive myelin probe that provides a direct means to detect myelin changes in the brain. Thus, it can be used as a myelin-imaging marker to monitor myelin pathology in vivo.

SUBMITTER: Wu C

PROVIDER: S-EPMC3044472 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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A novel PET marker for in vivo quantification of myelination.

Wu Chunying C Wang Changning C Popescu Daniela C DC Zhu Wenxia W Somoza Eduardo A EA Zhu Junqing J Condie Allison G AG Flask Christopher A CA Miller Robert H RH Macklin Wendy W Wang Yanming Y

Bioorganic & medicinal chemistry 20101109 24

C-11-labeled N-methyl-4,4'-diaminostilbene ([(11)C]MeDAS) was synthesized and evaluated as a novel radiotracer for in vivo microPET imaging of myelination. [(11)C]MeDAS exhibits optimal lipophilicity for brain uptake with a logP(oct) value of 2.25. Both in vitro and ex vivo staining exhibited MeDAS accumulation in myelinated regions such as corpus callosum and striatum. The corpus callosum region visualized by MeDAS is much larger in the hypermyelinated Plp-Akt-DD mouse brain than in the wild-ty ...[more]

PMID: 21071233

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Dataset Information

A novel PET marker for in vivo quantification of myelination.

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A novel PET marker for in vivo quantification of myelination.

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