Table 4.

PET imaging studies assessing TSPO tracers in dementias.

Disorder	Population	Radioligand	Main Findings	References
FTLD	5 FTLD vs. 8 HC	11C-PK11195	Significantly increased radioligand binding in cortical frontal, medial temporal and subcortical areas in FTLD group	Cagnin et al. (2004) [130]
FTDP-17	3 presymptomatic MAPT gene carriers vs. 4 HC	11C-DAA1106	11C-DAA1106 BPND greater in the medial frontal, occipital and in the posterior cingulate cortex of pre-symptomatic gene carriers than in healthy volunteers	Miyoshi et al. (2010) [131]
DLB	11 early-stage drug-naive DLB patients vs. 11 HC	11C-PK11195	DLB patients showed increased subcortical (basal ganglia, substantia nigra) and cortical (cerebellum) tracer BPND	Iannaccone et al. (2013) [54]
PDD	11 PDD patients vs. 10 HC	11C-PK11195	BPND significant increase in frontal, temporal, parietal and occipital cortical regions	Edison et al. (2013) [52]
PDD/AD	10 AD, 10 MCI, 11 PDD patients and 16 HC	11C-PK11195	Significantly increased tracer BPND in cortical and subcortical regions of AD, PDD and MCI patients compared with controls Significant negative correlation between MMSE and 11C-PK11195 BPND in temporoparietal, occipital and frontal cortex of AD and PDD patients	Fan et al. (2015) [125]
	9 PDD, 8 AD and 8 HC	11C-PK11195	Tracer was significantly increased in cortical regions of AD and PDD patients, compared to controls	Femminella et al. (2016) [132]
AD	8 AD patients vs. 15 HC	11C-PK11195	Significantly increased radioligand binding in the entorhinal, temporoparietal and cingulate cortex 1 patient with isolated memory impairment but without dementia exhibited an increase of 11C-PK11195 binding in the fusiform gyri, inferior temporal gyri and parahippocampus	Cagnin et al. (2001) [100]
	13 AD patients vs. 10 HC	11C-PK11195	Significantly increased tracer BPND in the cortical and subcortical regions in AD patients Tracer binding in gray matter and cortical regions negatively correlated with MMSE scores	Edison et al. (2008) [105]
	10 AD patients vs. 10 HC	11C-DAA1106	Significantly increased 11C-DAA1106 BPND in the cerebellum, cortical regions (prefrontal, lateral temporal, parietal and occipital cortex) and striatum in AD patients, compared to age-matched control subjects	Yasuno et al. (2008) [107]
	13 MCI patients vs. 10 HC	11C-PK11195	5/13 patients showed higher cortical tracer BPND than in controls Only frontal cortex radioligand uptake was significantly raised in MCI patients	Okello et al. (2009) [115]
	6 mild-moderate AD patients, 6 MCI patients and 5 HC	11C-PK11195	TSPO PET images showed no significant difference between the three groups	Wiley et al. (2009) [111]
	11 drug-naïve AD patients vs. 10 HC	11C-PK11195	Significantly increased 11C-PK11195 BPND in the medial frontal, parietal and left temporal cortex in the AD group Significant inverse correlation between MMSE score and 11C-PK11195 BPND in anterior cingulate cortex, precuneus and hippocampus	Yokokura et al. (2011) [106]
	6 AD patients vs. 12 HC	11C-vinpocetine	No significant difference between AD patients and age-matched control subjects in SUV of all brain regions	Gulyas et al. (2011) [133]
	10 AD, 7 MCI patients and 10 HC	11C-DAA1106	Mean BP values of MCI and AD patients higher than those of controls in prefrontal, parietal, temporal, occipital and cingulate cortex, striatum, cerebellum and thalamus No difference in binding was found between AD and MCI patients	Yasuno et al. (2012) [108]
	19 AD, 10 MCI patients and 13 HC	11C-PBR28	Significantly increased tracer binding in inferior parietal lobule, middle plus inferior temporal cortex and precuneus in AD patients, compared to MCI patients and HC EOAD patients had greater binding than LOAD	Kreisl et al. (2013) [109]
	19 probable AD, 10 MCI patients and 21 HC	11C-PK11195	ROI based analyses showed no differences between diagnostic groups, with large overlap between subject groups	Schuitemaker et al. (2013) [112]
	9 AD patients vs. 7 HC	18F-FEDAA1106	No significant change in 18F-FEDAA1106 binding between AD and HC	Varrone et al. (2013) [134]
	-8 AD patients vs. 8 HC -AD patients were followed-up for 16 months	11C-PK11195	-AD patients showed a mean increase of 30% radioligand BPND in frontal, temporal, parietal, occipital cortical regions, hippocampus and striatum -In parallel to cognitive deterioration, microglial activation was increased longitudinally in 6/8 AD patients	Fan et al. (2015) [103]
	25 AD patients, 11 MCI and 21 HC	11C-PBR28	AD patients showed greater radioligand VT/fP values than MCI patients and HC in combined middle, inferior temporal and entorhinal cortices	Lyoo et al. (2015) [102]
	10 AD patients vs. 7 HC	18F-FEMPA	Significantly higher radioligand VT in the medial temporal cortex in AD patients than in controls	Varrone et al. (2015) [135]
	18 AD patients in moderate stage vs. 21 HC	18F-FEPPA	Compared to HC, AD patients showed a significant increase in 18F-FEPPA binding in both, gray matter (hippocampus, temporal, prefrontal, parietal and occipital cortex) and white matter (cingulum bundle, posterior limb of the internal capsule) No statistical correlation between radioligand VT in white or gray matter and AD severity	Suridjan et al. (2015) [104]
	10 AD patients vs. 6 HC	18F-DPA-714	No significant difference in tracer BPND and VT in whole brain gray matter between AD patients and HC	Golla et al. (2015) [136]
	-14 AD patients vs. 8 HC -Follow-up of 2.5 years in AD patients	11C-PBR28	-Tracer binding (SUVr) significantly greater among patients than controls in inferior parietal lobule, precuneus, occipital cortex, hippocampus, entorhinal cortex and combined middle and inferior temporal cortex EOAD patients showed significantly higher TSPO radioligand binding than LOAD patients in several cortical regions (e.g., prefrontal and occipital cortex) -TSPO binding in temporoparietal areas increased from 3.9% to 6.3% per annum in patients, compared with only −0.5–1% per annum in controls	Kreisl et al. (2016) [101]
	-58 AD patients (34 MCI and 24 dementia) vs. 32 controls (24 HC and 8 amyloidosis-controls) -30 AD patients were followed-up over 2 years	18F-DPA-714	-In MAB + HAB group, tracer-GCI significantly higher in amyloidosis controls than in HC, especially in the cingulum and the precuneus Compared to controls, significantly increased tracer binding in temporal and parietal cortex in AD groups, even at the prodromal stage Significant positive correlation between the DPA-714-GCI and MMSE scores -GCI-DPA-714 SUVr greater in the slow decliners than in the fast decliners group	Hamelin et al. (2016) [110]

AD, Alzheimer’s disease; BP_ND, non-displaceable binding potential; CDR-SB, clinical dementia rating scale-sum of boxes; DLB, dementia with Lewy bodies; EOAD, early-onset AD; FTDP-17, frontotemporal dementia with parkinsonism linked to chromosome 17; FTLD, frontotemporal lobar degeneration; f_P, plasma-free fraction of radioligand; GCI, global cortical index; HAB, TSPO high affinity binders; HC, healthy control; LOAD, late-onset AD; MAB, TSPO mixed affinity binders, MCI, mild cognitive impairment; MMSE, mini-mental state examination; ROI, region of interest, SUVr, standard uptake value ratio; PPD, Parkinson’s disease dementia; V_T, total distribution volume.