TY - JOUR T1 - Direct imaging of hypermyelination in Plp-Akt-DD mouse model JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 553 LP - 553 VL - 51 IS - supplement 2 AU - Chunying Wu AU - Daniela Popescu AU - Chris Flask AU - Eduardo Somoza AU - Wenxia Zhu AU - Changning Wang AU - Robert Miller AU - Wendy Macklin AU - Yanming Wang Y1 - 2010/05/01 UR - http://jnm.snmjournals.org/content/51/supplement_2/553.abstract N2 - 553 Objectives To develop and evaluate molecular probes for in vivo imaging of myelin. Methods 1) radiosynthesis of [11C]DAS was carried out through radiomethylation using [11C]MeTfO with high radiochemical yield and purity; 2) Lipophilicity of [11C]DAS was determined by distribution between octanol and water; 3) Ex vivo autoradiography was conducted following i. v. injection; 4) Brain uptake and biodistribution were carried out in wild type mice; 5) In vivo quantitative microPET study in AKT knockout hypermyelinated mouse model were conducted to evaluate the in vivo pharmacokinetic profiles. Results [11C]DAS exhibits a optimal lipophilicity with a logPoct value of 2.25. Ex vivo autoradiography demonstrated that DAS readily entered the mouse brain and selectively labeled myelinated white matter regions. [11C]DAS demonstrated abundant initial brain uptake (2.56% injected dose/whole brain at 5 min) and prolonged retention in the brain (1.37% injected dose/whole brain at 60 min). Quantitative microPET study showed that accumulation of [11C]DAS in corpus callosum region in hypermyelinated mouse model was proportionally higher than that in normal control littermates, which was consistent with the level of myelination in the region as confirmed by subsequent in vitro histological studies. Conclusions We demonstrated that ([11C]DAS-PET imaging studies and subsequent quantitative analysis can directly differentiate hypermyelinated mice from control littermates based on brain retention of ([11C]DAS. These studies suggest that [11C]DAS-PET can be used as a surrogate marker of myelination in the brain ER -