RT Journal Article
SR Electronic
T1 Direct imaging of hypermyelination in Plp-Akt-DD mouse model
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 553
OP 553
VO 51
IS supplement 2
A1 Chunying Wu
A1 Daniela Popescu
A1 Chris Flask
A1 Eduardo Somoza
A1 Wenxia Zhu
A1 Changning Wang
A1 Robert Miller
A1 Wendy Macklin
A1 Yanming Wang
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/553.abstract
AB 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