Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord
Version of Record online: 23 SEP 2013
© 2013 American Neurological Association
Annals of Neurology
Volume 74, Issue 5, pages 688–698, November 2013
How to Cite
Wu, C., Zhu, J., Baeslack, J., Zaremba, A., Hecker, J., Kraso, J., Matthews, P. M., Miller, R. H. and Wang, Y. (2013), Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord. Ann Neurol., 74: 688–698. doi: 10.1002/ana.23965
- Issue online: 18 DEC 2013
- Version of Record online: 23 SEP 2013
- Accepted manuscript online: 1 JUL 2013 06:59AM EST
- Manuscript Accepted: 7 JUN 2013
- Manuscript Revised: 30 MAY 2013
- Manuscript Received: 23 FEB 2013
- Department of Defense . Grant Number: W81XWH-10-1-0842
- National Multiple Sclerosis Society . Grant Number: RG 4339-A-2
- NIH National Institute of Neurological Diseases and Stroke . Grant Number: R01 NS061837
- Medical Research Council
Novel therapeutic interventions aimed at myelin repair are now under development for neuroprotection as well as functional recovery of patients with multiple sclerosis. However, development of myelin repair therapy necessitates a noninvasive approach for measuring changes in myelin content in vivo in a quantitative fashion not yet possible using magnetic resonance imaging. For this reason, we developed a novel positron emission tomography (PET) probe, termed [11C]MeDAS, that is capable of longitudinally imaging central nervous system myelin content.
The binding properties of [11C]MeDAS for myelin were systematically evaluated by in vitro and in situ fluorescent staining of the spinal cord and the brain, and by in vivo competitive blocking studies. Longitudinal PET studies were conducted in 3 rat models involving acute focal neuroinflammation in the brain, lysophosphatidylcholine (LPC)-induced focal demyelination in the spinal cord, and experimental autoimmune encephalomyelitis (EAE). Image-guided myelin repair therapy was conducted in an LPC rat model using a mesenchymal stem cell-based hepatocyte growth factor (HGF). Biodistribution and acute toxicity studies of [11C]MeDAS were also conducted.
MeDAS selectively stains myelin in the spinal cord and brain. Neuroinflammation did not affect [11C]MeDAS uptake in the brain as long as the myelin sheaths remained intact. Longitudinal PET studies in LPC and EAE rat models demonstrate that [11C]MeDAS uptake changes correlate with associated myelin loss in the spinal cord. Furthermore, using [11C]MeDAS-PET, the efficacy of myelin repair therapy with HGF was longitudinally monitored in vivo.
[11C]MeDAS-PET is a promising imaging marker for monitoring myelin pathology in vivo, future applications of which in humans should be achievable. Ann Neurol 2013;74:688–698