Abstract Details

Title In Vivo micro-PET Imaging Demonstrates Diminished Microglial Activation after FTY720 Treatment in an Animal Model of Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 151

Objective

Background BACKGROUND: Normal appearing white (NAWM) and gray matter (NAGM) are important loci of neuronal damage and microglial activation in progressive MS. Evaluation of microglial activation in vivo has not been possible until the recent developments in PET imaging. This allows the in vivo detection of activated microglial cells within demyelinating lesions, but also in areas of the brain appearing normal in conventional MRI images. We have used a focal rat EAE model to evaluate the extent of microglial activation in acute lesions, in chronic inflammation, and in response to anti-inflammatory treatment.

Design/Methods DESIGN/METHODS: A focal EAE model of MS was used. Animals were imaged using radioligands [11C]PK11195 and [18F]GE180 binding to TSPO, a 18-kDa translocator protein expressed on activated microglial cells (but not on resting microglial cells). Some animals were killed for autoradiography at each for the five time points (n=13). Animals with chronic inflammation were treated for 14 days either with FTY720 at 0.3mg/kg/po/day or with placebo.

Results RESULTS: There was an increase in TSPO binding, maximally with [18F]GE180 at day 28. Ratio of lesion to contralateral hemisphere binding was 1.75±0.26. Autoradiography demonstrated similarly increased binding. FTY-treatment significantly reduced the lesion size when evaluated using in vivo micro-PET imaging and the TSPO-ligands; in the placebo-treated group the lesion size increased by 6 mm2 over the treatment period, whereas in the FTY720-treated group the lesion size was diminished by 15.1 mm2, p = 0.018, student's t-test.

Conclusions CONCLUSIONS: In vivo PET imaging using either [18F]GE-180 or [11C]PK11195 radioligand can be used to quantitate microglial activation in a focal EAE model in rat. Importantly, FTY720 treatment resulted with diminished microglial activation, which could be demonstrated using PET.

Authors/Disclosures
Laura Airas, MD, PhD (Turku University Hospital) PRESENTER	Dr. Airas has nothing to disclose.
	No disclosure on file
	No disclosure on file
Victoria Barghout, PhD	No disclosure on file
Daniel Anthony, PhD, MA (University of Oxford)	Dr. Anthony has received personal compensation for serving as an employee of University of Oxford. Dr. Anthony has received personal compensation for serving as an employee of Somerville College Oxford. Dr. Anthony has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Anthony has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Neuroplast. Dr. Anthony has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Oxomics. The institution of Dr. Anthony has received research support from Numares. The institution of Dr. Anthony has received research support from MRC UK.
Juha O. Rinne, MD, PhD	No disclosure on file

��ɫ��

��ɫ��