[11C]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis

Abstract

Background: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, often confirmed by magnetic resonance imaging. This image modality, however, is not ideal for discrimination of demyelination in grey and white matter regions from inflammatory lesions. Positron Emission Tomography (PET), using specific radiopharmaceuticals, can be a tool to differentiate between these processes. The radiopharmaceutical [¹¹C]PIB is widely used for detection of β-amyloid plaques, but has also been suggested for the analysis of myelin content due to its consistent uptake in white matter. The aim of this study was to evaluate [¹¹C]PIB PET imaging as a tool for detecting demyelinated regions in white and grey matter of non-human primate model of progressive MS.

Methods: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of recombinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [¹¹C]PIB PET images were acquired prior to immunization (baseline) and after symptoms were present (end of experiment). Brain tissue was isolated for histochemical analysis.

Results: All rhMOG/IFA-treated and rhMOG/CFA-treated animals showed clinical signs of EAE. The rhMOG/CFA group presented a significant [¹¹C]PIB uptake reduction only in the left motor cortex (9%, P = 0.011). For the rhMOG/IFA group, significant decrease in [¹¹C]PIB uptake was observed in the whole brain (15%, P = 0.015), in the right hemisphere of body of corpus callosum (34%, P = 0.02), splenium of corpus callosum (38%, P = 0.004), hippocampus (19%, P = 0.036), optic tract (13%, P = 0.025), thalamus (14%, P = 0.041), Globus pallidus (23%, P = 0.017), head of caudate nucleus (25%, P = 0.045), tail of caudate nucleus (29%, P = 0.003), putamen (28%, P = 0.047) and left hemisphere of body of corpus callosum (14%, P = 0.037) and head of caudate nucleus (23%, P = 0.023). [¹¹C]PIB uptake significantly correlated with luxol fast blue histology (myelin marker), both in the rhMOG/IFA (r²= 0.32, P < 0.0001) and the rhMOG/CFA group (r²= 0.46, P < 0.0001).

Conclusion: [¹¹C]PIB PET imaging is an efficient tool for detecting demyelination in grey and white matter, in a non-human primate model of progressive MS.

Keywords: EAE marmoset model; Multiple sclerosis; PET imaging; Pittsburgh compound B.