TY - JOUR
T1 - Translocator protein PET imaging for glial activation in multiple sclerosis
AU - Oh, Unsong
AU - Fujita, Masahiro
AU - Ikonomidou, Vasiliki N.
AU - Evangelou, Iordanis E.
AU - Matsuura, Eiji
AU - Harberts, Erin
AU - Ohayon, Joan
AU - Pike, Victor W.
AU - Zhang, Yi
AU - Zoghbi, Sami S.
AU - Innis, Robert B.
AU - Jacobson, Steven
N1 - Funding Information:
Acknowledgement We thank Maria Ferraris Araneta (MIB/NIMH) and Kaylan Fenton (NIB/NINDS) for clinical support. This research was supported by the Intramural Research Program of the NIH (NINDS and NIMH).
PY - 2011/9
Y1 - 2011/9
N2 - Glial activation in the setting of central nervous system inflammation is a key feature of the multiple sclerosis (MS) pathology. Monitoring glial activation in subjects with MS, therefore, has the potential to be informative with respect to disease activity. The translocator protein 18 kDa (TSPO) is a promising biomarker of glial activation that can be imaged by positron emission tomography (PET). To characterize the in vivo TSPO expression in MS, we analyzed brain PET scans in subjects with MS and healthy volunteers in an observational study using [11C]PBR28, a newly developed translocator protein-specific radioligand. The [11C]PBR28 PET showed altered compartmental distribution of TSPO in the MS brain compared to healthy volunteers (p = 0.019). Focal increases in [11C]PBR28 binding corresponded to areas of active inflammation as evidenced by significantly greater binding in regions of gadolinium contrast enhancement compared to contralateral normal-appearing white matter (p = 0.0039). Furthermore, increase in [11C]PBR28 binding preceded the appearance of contrast enhancement on magnetic resonance imaging in some lesions, suggesting a role for early glial activation in MS lesion formation. Global [11C]PBR28 binding showed correlation with disease duration (p = 0.041), but not with measures of clinical disability. These results further define TSPO as an informative marker of glial activation in MS.
AB - Glial activation in the setting of central nervous system inflammation is a key feature of the multiple sclerosis (MS) pathology. Monitoring glial activation in subjects with MS, therefore, has the potential to be informative with respect to disease activity. The translocator protein 18 kDa (TSPO) is a promising biomarker of glial activation that can be imaged by positron emission tomography (PET). To characterize the in vivo TSPO expression in MS, we analyzed brain PET scans in subjects with MS and healthy volunteers in an observational study using [11C]PBR28, a newly developed translocator protein-specific radioligand. The [11C]PBR28 PET showed altered compartmental distribution of TSPO in the MS brain compared to healthy volunteers (p = 0.019). Focal increases in [11C]PBR28 binding corresponded to areas of active inflammation as evidenced by significantly greater binding in regions of gadolinium contrast enhancement compared to contralateral normal-appearing white matter (p = 0.0039). Furthermore, increase in [11C]PBR28 binding preceded the appearance of contrast enhancement on magnetic resonance imaging in some lesions, suggesting a role for early glial activation in MS lesion formation. Global [11C]PBR28 binding showed correlation with disease duration (p = 0.041), but not with measures of clinical disability. These results further define TSPO as an informative marker of glial activation in MS.
KW - Glial activation
KW - Multiple sclerosis
KW - PET
KW - Translocator protein
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U2 - 10.1007/s11481-010-9243-6
DO - 10.1007/s11481-010-9243-6
M3 - Article
C2 - 20872081
AN - SCOPUS:79960594561
SN - 1557-1890
VL - 6
SP - 354
EP - 361
JO - Journal of Neuroimmune Pharmacology
JF - Journal of Neuroimmune Pharmacology
IS - 3
ER -