Introduction
Methods
Search strategy
Inclusion criteria
Results
Year | Reference | Study population | PET tracer | Molecular target | Main findings |
---|---|---|---|---|---|
Brain metabolism | |||||
1997 | [15] | 7 HD, 7 HCs | [15O]H2O | Regional cerebral blood flow | Deficit in the task-related activation in the striatum and its frontal motor area projections |
1990 | [19] | 23 HD, 21 HCs | [18F]FDG | Glucose uptake | Decrease in caudate and cortical metabolism. Correlation with cognitive dysfunction |
1996 | [17] | 8 HD, 10 pre-HD, previous HCs | [18F]FDG, [11C]raclopride | Glucose uptake, D2 receptors | Lower loss of glucose uptake than of D2 receptor levels (2.3 % vs. 6.3 % per year) |
2006 | [23] | 47 HD, 24 pre-HD, 30 HCs | [18F]FDG | Glucose uptake | Decrease in caudate and cortical metabolism in HD patients and in pre-HD patients. Hypometabolism in pre-HD patients preceded volume loss |
2012 | [24] | 46 pre-HD | [18F]FDG | Glucose uptake | Lower caudate metabolism in patients with pre-HD converted to HD than in patients with pre-HD not converted (5-years follow-up) |
2013 | [28] | 12 pre-HD, 12 HCs | [18F]FDG, [11C]raclopride | Glucose uptake, D2 receptors | Progressive alterations of striatothalamic and cortical metabolic activity network in pre-HD patients |
Dopaminergic function | |||||
1994 | [36] | 5 HD, 1 pre-HD, 5 HCs | [11C]SCH 23390 | D1 receptors | Decrease (75 %) in striatal D1 receptors density in HD patients |
1995 | [39] | 10 HD patients, 9 HCs | [11C]SCH 23390, [11C]raclopride | D1 receptors, D2 receptors | Decrease in striatal D1 and D2 receptors in HD patients. Akinetic-rigid patients had greater D1 and D2 receptor loss in the striatum than choreic HD patients |
1997 | [33] | 5 HD, 5 HCs | [11C]SCH 23390, [11C]raclopride, [11C]β-CIT | D1 receptors, D2 receptors, DAT | Decrease in striatal D1 and D2 receptors and striatal DAT binding. Correlation between D2 receptor loss and duration of symptoms |
1998 | [45] | 8 HD, 10 pre-HD | [11C]Raclopride | D2 receptors | Decrease in D2 receptors in the striatum of pre-HD patients. Correlation between D2 receptor loss and CAG repeat length |
1998 | [43] | 17 pre-HD | [11C]SCH 23390, [11C]raclopride | D1 receptors, D2 receptors | Decrease in striatal D1 and D2 receptors in pre-HD patients. Correlation between D1 and D2 receptor loss and cognitive dysfunction |
1999 | [37] | 4 HD, 9 pre-HD, 7 HCs | [11C]SCH 23390, [11C]raclopride | D1 receptors, D2 receptors | Decrease in striatal D1 and D2 receptors in pre-HD patients. Correlation between D1 and D2 receptor loss and UHDRS |
2000 | [34] | 19 HD, 64 HCs | [11C]DTBZ | VMAT2 | Decrease in VMAT2 binding in caudate (30 %) and putamen (60 %) |
2005 | [38] | 27 pre-HD | [11C]Raclopride, [18F]FDG | D2 receptors, glucose uptake | Decrease (50 %) in D2 receptors in the striatum of pre-HD patients. Correlation between D2 receptor loss and increases in the product of age and CAG repeat length |
2006 | [40] | 12 HD, previous HCs | [11C]Raclopride | D2 receptors | Decrease in D2 receptors in the amygdala, and temporal and frontal cortex in HD patients |
2008 | [44] | 9 HD, 10 pre-HD, 10 HCs | [11C]Raclopride, [11C]PK11195 | D2 receptors, TSPO | Decrease in D2 receptors in the hypothalamus of HD and pre-HD patients. Correlation between D2 receptor loss and increased activation of microglia |
2010 | [42]a
| 16 HD, 11 pre-HD, previous HCs | [11C]Raclopride | D2 receptors | Decrease in D2 receptors in the cortex of HD and pre-HD patients. Correlation between D2 receptor cortical levels and cognitive dysfunction |
2011 | [35] | 9 HD, 9 HCs | [11C]FLB457 | D2 receptors | Decrease in D2 receptors in the striatum but not in extrastriatal areas. Correlation between striatum D2 receptor loss and motor symptoms |
Activation of microglia | |||||
2006 | [51]a
| 11 HD, 10 HCs | [11C]PK11195, [11C]raclopride | TSPO, D2 receptors | Increase in activation of microglia in striatal and cortical areas in HD patients. Correlation between increased TSPO and loss of D2 receptors in the striatum and with motor dysfunction (UHDRS) |
2007 | [52]a
| 11 pre-HD, 10 HCs | [11C]PK11195, [11C]raclopride | TSPO, D2 receptors | Increase in activation of microglia in striatal and cortical areas in pre-HD patients. Correlation between increased TSPO and loss of D2 receptors in the striatum |
2011 | [53]a
| 8 pre-HD, 8 HCs | [11C]PK11195, [11C]raclopride | TSPO, D2 receptors | Increase in activation of microglia in striatal and cortical areas in pre-HD patients. Correlation between increased TSPO in associative striatum and cognitive dysfunction |
2015 | [54]a
| 12 pre-HD, 12 HCs | [11C]PK11195 | TSPO | Increase in activation of microglia in cortical regions, basal ganglia and thalamic region in pre-HD patients. Correlation between increased TSPO and plasma levels of IL-1β, IL-6, IL-8 and TNF-α. First in vivo evidence of an association between peripheral and central immune responses in pre-HD patients |
PDE10A | |||||
2014 | [59] | 5 HD, 11 HCs | [18F]JNJ42259152 | PDE10A | Decreases in PDE10A of 70.7 % and 62.6 % in the caudate and putamen, respectively. No correlations between PDE10A and clinical scales |
2014 | [60] | 8 HD, 3 pre-HD, 9 HCs | [18F]MNI-659 | PDE10A | Decreases in PDE10A of 50 % in the striatum of manifest HD patients compared with HCs. Pre-HD patients had values intermediate between HD patients and HCs. Striatal correlations between PDE10A and severity of disease measured by the clinical scale (UHDRS, motor subscale), the molecular marker (BOP), and regional atrophy |
2015 | [61] | 12 pre-HD, 12 HCs | [11C]IMA107 | PDE10A | Decreases in PDE10A of 30 % in the striatum and 25 % in the pallidus, and increase of 35 % in motor thalamic nuclei in pre-HD patients |
Adenosine and cannabinoid receptors | |||||
2014 | [64] | 8 HD, 6 pre-HD-Bb, 7 pre-HD-Ac, 36 HCs | [18F]CPFPX | A1 receptors | Cerebral A1 receptor levels in pre-HD-A patients were higher than in HCs (by up to 31 % in the thalamus). Successive reduction in A1 receptor binding in pre-HD-B patients compared with HCs and binding in manifest HD patients lower than in HCs (decrease to 25 % in the caudate and amygdala). Strong correlation between A1 receptor binding and years since onset |
2010 | [73] | 20 HD, 14 HCs | [18F]MK-9470, [18F]FDG | CB1 receptors, glucose uptake | Decrease in CB1 receptors in the cerebrum and cerebellum (grey matter) and brainstem |
Opioid and GABA receptors | |||||
1993 | [71] | 6 HD, 6 HCs | [11C]Flumazenil, [18F]FDG | GABA receptors, glucose uptake | Decrease in GABA receptors in the caudate and decrease in glucose uptake in the caudate putamen and thalamus |
2000 | [72] | 10 HD, 13 pre-HD | [11C]Flumazenil, [18F]FDG, [11C]raclopride | GABA receptors, glucose uptake, D2 receptors | Decrease in GABA receptors in the caudate and decrease in glucose uptake and D2 receptors in the caudate, putamen and thalamus in HD patients. Reduction in GABA receptors was significantly less in manifest HD patients than in pre-HD patients with normal D2 receptor levels, but not in comparison with pre-HD patients with reduced D2 receptor levels |
1997 | [77] | 2 HD, 9 HCs | [11C]Diprenorphine | Opioid receptors | Decrease in opioid receptors in the caudate and putamen |
Brain metabolism
Dopaminergic function
Activation of microglia
Phosphodiesterases
Adenosine and cannabinoid receptors
Opioid and GABA receptors
Progression monitoring
Brain target | Tracer | Caudate | Putamen | Thalamus | Globus pallidus | Frontal | Parietal | Temporal | Occipital |
---|---|---|---|---|---|---|---|---|---|
Brain metabolism | [18F]FDG | − | − | + | NE | − | − | − | + |
D1 receptors | [11C]SCH 23390 | − | − | NE | NE | = | NE | −b
| NE |
D2 receptors | [11C]Raclopride | − | − | NE | NE | −b
| NE | −b
| = |
Activation of microglia | [11C]PK11195 | + | + | = | + | + | + | = | = |
PDE10A | [18F]JNJ42259152 | − | − | +a
| − | NE | NE | NE | NE |
[18F]MNI-659 | |||||||||
[11C]IMA107 | |||||||||
A1 adenosine receptors | [18F]CPFPX | − | − | − | NE | − | − | − | = |
CB1 receptors | [18F]MK-9470 | − | − | NE | NE | NE | NE | NE | NE |
OPIOID receptors | [11C]Diprenorphine | − | − | + | NE | + | NE | − | = |
GABA receptors | [11C]Flumazenil | − | = | = | = | = | = | = | = |