Table 7.
PET imaging studies assessing TSPO tracers in multiple sclerosis.
| Population | Radioligand | Main Findings | References |
|---|---|---|---|
| 2 RR patients | 11C-PK11195 | Increased 11C-PK11195 BPND in MRI-defined active MS lesions, not in chronic lesions | Vowinckel et al. (1997) [213] |
| 12 MS patients (8 RR, 1 SP and 3 PP), 8 HC | 11C-PK11195 | Increased global and in MRI-defined (T1/T2) active lesions radioligand BPND in MS patients Greater brainstem and thalamus tracer BPND in MS patients than in HC Patient with a history of optic neuritis showed 11C-PK11195 signals in the lateral geniculate bodies (to which the optic nerve projects) |
Banati et al. (2000) [210] |
| 22 MS patients (13 RR, 7 SP and 2 PP), 7 HC | 11C-PK11195 | No statistical difference in NAWM and GM tracer BPND was found between MS patients and healthy volunteers Tracer BPND significantly greater in gadolinium lesions than in NAWM A higher 11C-PK11195 BPND was found in both situations, clinical relapse or presence of T1-gadolinium lesions Statistical correlation found between higher 11C-PK11195 BPND and disease duration |
Debruyne et al. (2003) [199] |
| 22 MS patients (13 RR, 7 SP and 2 PP), 8 HC | 11C-PK11195 | NAWM tracer BPND was positively correlated with amount of brain atrophy Significant negative correlation between T2 lesions tracer BPND and brain atrophy |
Versijpt et al. (2005) [214] |
| 11 MS (mostly RR) patients vs. 7 HC | 11C-PBR28 | No statistical difference in neither WM fraction or GM fraction VT tracer between MS and healthy volunteers Gadolinium-enhancing lesions demonstrated significantly higher 11C-PBR28 binding than contralateral NAWM Global VT tracer showed correlation with disease duration but not with clinical disability |
Oh et al. (2011) [203] |
| 18 MS patients (10 RR and 8 SP), 8 HC | 11C-PK11195 | Proportion of abnormal high total cortical GM 11C-PK11195 BPND was greater in SP than in RR patients Mean total WM radioligand BPND was greater in SP than in RR patients SP patients showed additionally increased tracer BPND in precentral, superior parietal, lingual and anterior superior, median and inferior temporal gyri The 2 patients with the more active RR had the highest total cortical GM tracer BPND |
Politis et al. (2012) [198] |
| 9 RR untreated patients Patients were rescanned after 1 year of GA |
11C-PK11195 | The patient with the more active RR had the highest 11C-PK11195 BPND on the baseline TSPO PET scan Tracer BPND per unit volume statistically decreased in the whole brain and especially in the following regions: supratentorial brain, infratentorial brain, cerebral white matter, cortical gray matter, thalamus and putamen |
Ratchford et al. (2012) [204] |
| 9 RR in acute relapse (6 without treatment and 3 interferon-β treated) vs. 5 HC | 18F-FEDAA1106 | Similar radioligand BPND and VT between normal controls and MS patients No significant difference of BPND or VT between MS patients without treatment, MS patients with interferon-β treatment and healthy volunteers |
Takano et al. (2013) [215] |
| 11 RR vs. 11 HC | 18F-PBR111 | Increased tracer uptake in WM lesions and perilesional WM relative to HC Increased 18F-PBR111 VT was higher in lesions and perilesional volumes in MS patients compared to the NAWM of the same subjects Significant positive correlation between radioligand VT and MS score severity |
Colasanti et al. (2014) [205] |
| 19 MS patients (10 RR, 8 SP and 1 PP) | 11C-PK11195 | Black holes tracer BPND was greater in progressive patients than in RR patients In RR patients, significant inverse correlation between volume and 11C-PK11195 BPND of black holes was found Black holes tracer BPND was correlated with the EDSS in progressive patients |
Giannetti et al. (2014) [206] |
| 10 SP patients vs. 8 HC | 11C-PK11195 | Relative to controls, significantly increased tracer DVR was found in periventricular NAWM and thalamus of SP patients A pattern of increased TSPO density in the periplaque area surrounding the borders of chronic plaques was observed In active plaques with gadolinium-enhancement increased TSPO binding was found in the core of the lesion but not in the area surrounding them |
Rissanen et al. (2014) [202] |
| 18 CIS patients vs. 8 HC | 11C-PK11195 | Compared to controls, significantly increased tracer BPND was found in NAWM of CIS patients, while no difference was observed in GM In CIS patients with T2 MRI lesions, NAWM tracer BPND correlated with EDSS CIS patients who developed MS at 2 years had higher 11C-PK11195 BPND at baseline |
Giannetti et al. (2015) [206] |
| 5 RR patients (4 stable and 1 drug naive with active RR) vs. 4 HC | 11C-PBR28 | VT was similar between stable MS and healthy volunteers across whole brain and GM/WM/NAWM regional areas (frontal, parietal, temporal and occipital) Focal increases in tracer VT were observed at some areas corresponding to gadolinium-enhancing lesion of active MS patients |
Park et al. (2015) [216] |
| 9 RR patients vs. 8 HC | 18F-GE180 | Whole WM uptake (SUVRGM) slightly higher in RR patients than in HC Increased tracer uptake in inactive WM lesions and a further increase in gadolinium-enhancing lesions (Preliminary data) |
Trigg et al. (2015) [217] |
| 11 RR patients (6 with MDE) vs. 22 HC | 18F-PBR111 |
18F-PBR111 DVR higher in the hippocampus of MS patients relative to normal subjects, while no difference was observed in thalamus Hippocampal radioligand binding was correlated to BDI scores in MS patients and was highest in MS patients with current MDE |
Colasanti et al. (2016) [218] |
| 23 MS patients (16 RR and 7 SP) | 11C-PBR28 | No significant correlation between 11C-PBR28 DVR and EDSS in either WM lesions, NAWN or GM | Datta et al. (2016) [211] |
| 27 MS patients (12 RR and 15 SP), 14 HC | 11C-PBR28 | Compared to controls, significantly increased tracer DVR across the brain was found in MS cases; the greatest increases being in cortex and cortical lesions, thalamus, hippocampus and NAWM Relative to the same brain regions, radioligand uptake was greater in SPMS than in RRMS, except for cortical lesions (same TSPO levels) In MS patients, EDSS correlated positively with increased tracer SUVR in the NAWM, WM lesions, thalamus, hippocampus and basal ganglia |
Herranz et al. (2016) [200] |
BPND, binding potential; BDI, beck depression inventory; CIS, clinically isolated syndrome; DVR, distribution volume ratio; EDSS, expanded disability status scale; GA, glatiramer acetate; GM, gray matter; HC, healthy control; MDE, major depressive disorder; MS, multiple sclerosis; NAGM, normal-appearing gray matter; NAWM, normal-appearing white matter; PP, primary progressive multiple sclerosis; RR, relapse-remitting multiple sclerosis; SP, secondary progressive multiple sclerosis; SUVR, standardized uptake value ratio; VT, total volume of distribution; WM, white matter.