16366
doi
10.2967/jnumed.113.131698
oai:zenodo.org:16366
user-inmind
user-eu
Tuisku, Jouni
Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
Rokka, Johanna
Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
Paavilainen, Teemu
Medical Imaging Centre of Southwest Finland, Turku University Hospital and University of Turku, Turku, Finland
Parkkola, Riitta
Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland and Department of Radiology, University Hospital of Tampere, Tampere, Finland
Rinne, Juha O
Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland
Airas, Laura
Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland
In Vivo Detection of Diffuse Inflammation in Secondary Progressive Multiple Sclerosis Using PET Imaging and the Radioligand 11C-PK11195.
Rissanen, Eero
Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland and Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland
info:eu-repo/semantics/restrictedAccess
multiple sclerosis
disease progression
microglia
PET
<p>Patients with secondary progressive multiple sclerosis (SPMS) are lacking efficient medication to slow down the progression of their disease. PET imaging holds promise as a method to study, at the molecular level and in vivo, the central nervous system pathology of SPMS. PET might thus help to elucidate potential therapeutic targets and be useful as an imaging biomarker in future treatment trials of progressive multiple sclerosis. The objective of this study was to evaluate whether translocator protein (TSPO) imaging could be used to visualize the diffuse inflammation located in the periplaque area and in the normal-appearing white matter (NAWM) in the brains of patients with SPMS.</p>
<p>METHODS: This was an imaging study using MR imaging and PET with 11C-PK11195 binding to TSPO, which is expressed in activated, but not in resting, microglia. Ten SPMS patients with a mean expanded disability status scale score of 6.3 (SD, 1.5) and eight age-matched healthy controls were studied. The imaging was performed using High-Resolution Research Tomograph PET and 1.5-T MR imaging scanners. Microglial activation was evaluated as the distribution volume ratio (DVR) of 11C-PK11195 from dynamic PET images. DVR estimations were performed with special interest in NAWM and gray matter using region-of-interest and parametric image-based approaches.</p>
<p>RESULTS: The DVR of 11C-PK11195 was significantly increased in the periventricular and total NAWM (P = 0.016 and P < 0.001, respectively) and in the thalamic ROIs (P = 0.027) of SPMS patients, compared with the control group. Similarly, parametric image analysis showed widespread increases of 11C-PK11195 in the white matter of SPMS patients, compared with healthy controls. Increased perilesional TSPO uptake was present in 57% of the chronic T1 lesions in MR imaging.</p>
<p>CONCLUSION: The finding of increased 11C-PK11195 binding in the NAWM of SPMS patients is in line with the neuropathologic demonstration that activated microglial cells are the source of diffuse NAWM inflammation. Evaluating microglial activation with TSPO-binding PET ligands provides a unique tool to assess diffuse brain inflammation and perilesional activity in progressive multiple sclerosis in vivo.</p>
Zenodo
2014-04-07
info:eu-repo/semantics/article
608933
user-inmind
user-eu
award_title=Imaging of Neuroinflammation in Neurodegenerative Diseases; award_number=278850; award_identifiers_scheme=url; award_identifiers_identifier=https://cordis.europa.eu/projects/278850; funder_id=00k4n6c32; funder_name=European Commission;
1579526998.082799
public
J Nucl Med.
55
6
939-944
2014-04-07