Table 1.
Key positron emission tomography imaging studies in Huntington’s disease
| Ref. | Subjects | PET radiopharmaceutical | Main findings |
| Dopaminergic system | |||
| Ginovart et al[56], 1997 | 5 HD patients | 11C-b-CIT | 50% decrease in striatal dopamine transporter (DAT) binding. |
| 5 HCs | 11C-SCH23390 11C-raclopride | 40% decrease in striatal D1 and D2 receptors binding. D1 and D2 binding in the striatum was significantly associated with the duration of symptoms | |
| Reduced D1 receptors binding in the temporal cortex | |||
| Bohnen et al[57], 2000 | 19 HD patients 64 HCs | 11C-DTBZ | Reduced nigrostriatal density of VMAT2 (caudate: 33%, putamen: 56%-75%) |
| Sedvall et al[58], 1994 | 5 HD patients | 11C-SCH 23390 | 75% reduction in striatal D1 receptor density in HD patients |
| 1 premanifest HD gene carrier 5 HCs | D1 binding in the premanifest HD gene carrier was in the lower range of the HCs | ||
| Turjanski et al[55], 1995 | 10 HD patients 9 HCs for 11C-raclopride and 6 HCs for 11C-SCH 23390 | 11C-SCH 2339011C-raclopride | Parallel reduction of striatal D1 and D2 receptor binding (31%-39%) with greater loss of mean striatal D1 and D2 binding in the akinetic-rigid patients than those choreic patients without rigidity |
| Lawrence et al[60], 1998 | 17 premanifest HD gene carriers | 11C-SCH 23390 11C-raclopride | Correlation between striatal D1 and D2 receptors binding and cognitive performance |
| Pavese et al[61], 2003 | 12 HD patients | 11C-raclopride | 4.8% annual reduction in striatal D2 receptor binding |
| HCs from previous studies | D2 reduction receptor density in extrastriatal regions including amygdala, temporal and frontal cortex | ||
| Andrews et al[64], 1999 | 9 premanifest HD gene carriers 4 HD patients | 11C-SCH 23390 11C-raclopride | Mean annual loss of D1 and D2 binding of 2% and 4% respectively in the group of asymptomatic HD gene carriers |
| 7 HCs 3 subjects at risk for HD | Mean annual loss of D1 binding of 5% and D2 binding of 3% in symptomatic HD patients | ||
| UHDRS motor scores and TFC correlated with PET measures of striatal dopamine receptor in both groups | |||
| Premanifest HD gene carriers with active progression had an increased mean annual loss of D1 and D2 receptor binding (5% and 6.5% respectively) | |||
| Pavese et al[62], 2010 | 16 HD patients11 premanifest HD gene carriers | 11C-raclopride | 62.5% of symptomatic HD patients and 54.5% of premanifest carriers showed cortical reductions in D2 binding |
| HCs from previous studies | HD patients with decreased cortical D2 binding had worse scores on | ||
| neuropsychological tests assessing attention and executive functions than subjects without cortical dopamine dysfunction | |||
| Antonini et al[66], 1998 | 10 premanifest gene carriers 8 HD patients | 11C-raclopride | Correlation between CAG repeat length and the estimated percentage loss of striatal D2 binding after age correction in premanifest HD gene carriers and HD patients |
| Rate of disease progression is faster during the earlier asymptomatic stages of the disease | |||
| Brain activation and metabolism | |||
| Antonini et al[65], 1996 | 10 premanifest HD gene carriers | 18F-FDG 11C-raclopride | Annual loss of 2.3% in striatal glucose metabolism and 6.3% annual decline in D2 receptor binding |
| 8 HD patients | |||
| HCs from previous studies | |||
| Kuwert et al[75], 1990 | 23 HD patients 21 HCs | 18F-FDG | Decreases of caudate and regional cortical metabolism correlated with cognitive decline |
| Ciarmiello et al[79], 2006 | 24 premanifest HD gene carriers47 HD patients | 18F-FDG | Significant decrease in glucose uptake in the cortex (frontal and temporal lobes) and striatum in both premanifest HD gene carriers and HD patients |
| 30 HCs | Striatal and cortical hypometabolism in premanfest HD gene carriers precedes neuronal loss | ||
| Ciarmiello et al[80], 2012 | 43 premanifest HD gene carriers | 18F-FDG | Premanifest HD gene carriers who phenoconverted after five years from the PET scan had a mean glucose uptake in the caudate significantly lower than the those who remained symptom-free after five years |
| Weeks et al[83], 1997 | 7 HD patients 7 HCs | H215O | Impaired activation of the striatum and its frontal motor projection areas during motor tasks such as paced joystick movements |
| Tang et al[87], 2013 | 12 premanifest HD gene carriers 12 HCs | 18F-FDG 11C-raclopride | Network analysis showed a significant spatial covariance pattern characterized by progressive changes in striato-thalamic and cortical metabolic activity network activity increased linearly over 7 yr and was not influenced by intercurrent phenoconversion |
| Neuroinflammation and activated microglia | |||
| Pavese et al[99], 2006 | 11 HD patients 10 HCs | 11C-PK11195 11C-raclopride | Significant microglial activation in the striatum and cortical regions of HD patients |
| Striatal 11C-PK11195 binding correlates with loss of striatal dopamine D2 binding | |||
| Striatal 11C-PK11195 binding correlated with UHDRS scores | |||
| Tai et al[100], 2007 | 11 premanifest HD gene carriers | 11C-PK11195 11C-raclopride | Increased striatal and cortical microglial activation in premanifest HD gene carriers |
| 10 HCs | Higher striatal 11C-PK11195 binding correlated with lower striatal D2 binding | ||
| Politis et al[101], 2011 | 8 premanifest HD gene carriers 8 HCs (11C-raclopride) 8 HCs (11C-PK11195) | 11C-PK11195 11C-raclopride | Increased levels of activated microglia in areas of the striatum associated with cognition and other areas related to cognitive function |
| Levels of microglial activation correlated with clinical scales of disease severity and motor dysfunction and with a higher probability of HD onset over the next 5 yr | |||
| Cannabinoid system | |||
| Van Laere et al[111], 2010 | 20 HD patients 14 HCs | 18FMK-9470 | Decrease of CB1 availability throughout the gray matter of the cerebrum, cerebellum, and brain stem in HD patients. |
PET: Positron emission tomography; HD: Huntington’s disease.