Abstract
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Objectives: To develop and evaluate molecular probes for in vivo imaging studies of myelin.
Methods: 1) brain uptake was quantitatively determined following i.v.tail injection; 2) in vitro staining of brain tissue sections was evaluated for specificity of binding to myelin sheaths; 3) ex vivo staining in both wild type and cuprizone-treated mice was characterized for in situ binding specificity; 4) radioligand-based binding assays were conducted to quantitatively determine binding affinities for myelin fractions; 5) in vivo quantitative microPET study in rat model of demyelination were conducted to evaluate the in vivo pharmacokinetic profiles.
Results: (E,E)-1,4-bis(4’-aminostyryl)-2-dimethoxy-benzene, termed BDB, was synthesized. Radioligand-based binding assays suggested that BDB exhibited a myelin-binding affinity in low micromole concentrations. In vitro staining showed that BDB selectively stains intact myelinated regions in wild-type mouse brain and lack of BDB staining was observed in myelin-deficient quaking mouse brain. Ex vivo tissue staining demonstrated that BDB could also delineate demyelinating lesions induced by cuprizone-treatment in mouse brain. Its initial brain entry was peaked at 5 min and then decreased gradually. MicroPET study in rat model of demyelination showed a accumulation pattern that is consistent with the level of myelination in normal brain regions compared to regions of demyelination.
Conclusions: BDB is an promising radioligand for PET imaging of myelination in the brain.
- Society of Nuclear Medicine, Inc.