Abstract
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Objectives: The formation of focal demyelinated lesions and progressive failure of remyelination in the central nervous system is the main characteristic of multiple sclerosis (MS). Conventional clinical imaging techniques are not quantitative for monitoring these demyelination and remyelination processes. In the present study, we investigated the validation of [18F]-BF227 PET imaging for quantitatively evaluating these processes in the rat model of MS.
Methods: Sprague-Dawley rats were stereotactically injected with lysolecithin into the right corpus callosum, and saline into the contralateral site. Static [18F]-BF227 PET imaging followed by T2-weighted MRI images were performed 7 days (demyelination group) or 28 days (remyelination group) after lysolecithin injection, in association with ex vivo autoradiography and in vitro histological myelin staining by Sudan black B.
Results: MicroPET images showed a higher uptake of [18F]-BF227 in the white matter than in the gray matter in MRI-derived different brain regions. The longitudinal study (Figure 1A) revealed that [18F]-BF227 uptake significantly increased in the remyelination group and not in the demyelination group (P = 0.021). The level of [18F]-BF227 uptake calculated, by ex vivo autoradiography in both groups, correlated well with the optical density of the lesions in the same sections via the semi-quantitative measurement of Sudan black B staining (Figure 1B, r = 0.768, P = 0.026).
Conclusion: [18F]-BF227 PET is adapted to the monitoring of demyelination and remyelination processes in the rat model of MS. These encouraging results justify further studies to prepare a PET neuroimaging study in MS patients. Research Support: