Skip to main content

PET in Huntington’s Disease

  • Chapter
  • First Online:
Book cover PET and SPECT in Neurology
  • 2406 Accesses

Abstract

From the 1980s onwards, PET molecular imaging has yielded a wealth of information on the molecular and structural biology of neurodegeneration in patients with Huntington’s disease. While currently not in use for day to day diagnostic or predictive clinical purposes in patients, it may acquire new relevance. In this review I will outline its applications to the study of human preclinical and clinical disease, to our understanding of the neurobiology of Huntington’s, as well as in the field of experimental therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andrews TC, Weeks RA, Turjanski N et al (1999) Huntington’s disease progression. PET and clinical observations. Brain 122(Pt 12):2353–2363

    Article  PubMed  Google Scholar 

  • Antonini A, Leenders KL, Spiegel R et al (1996) Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington’s disease. Brain 119(Pt 6):2085–2095

    Article  PubMed  Google Scholar 

  • Antonini A, Leenders KL, Eidelberg D (1998) [11C]raclopride-PET studies of the Huntington’s disease rate of progression: relevance of the trinucleotide repeat length. Ann Neurol 43:253–255

    Article  CAS  PubMed  Google Scholar 

  • Bachoud-Levi AC, Deglon N, Nguyen JP et al (2000a) Neuroprotective gene therapy for Huntington’s disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF. Hum Gene Ther 11:1723–1729

    Article  CAS  PubMed  Google Scholar 

  • Bachoud-Levi AC, Remy P, Nguyen JP et al (2000b) Motor and cognitive improvements in patients with Huntington’s disease after neural transplantation. Lancet 356:1975–1979

    Article  CAS  PubMed  Google Scholar 

  • Backman L, Robins-Wahlin TB, Lundin A et al (1997) Cognitive deficits in Huntington’s disease are predicted by dopaminergic PET markers and brain volumes. Brain 120(Pt 12):2207–2217

    Article  PubMed  Google Scholar 

  • Berent S, Giordani B, Lehtinen S et al (1988) Positron emission tomographic scan investigations of Huntington’s disease: cerebral metabolic correlates of cognitive function. Ann Neurol 23:541–546

    Article  CAS  PubMed  Google Scholar 

  • Boecker H, Kuwert T, Langen KJ et al (1994) SPECT with HMPAO compared to PET with FDG in Huntington disease. J Comput Assist Tomogr 18:542–548

    Article  CAS  PubMed  Google Scholar 

  • Bohnen NI, Koeppe RA, Meyer P et al (2000) Decreased striatal monoaminergic terminals in Huntington disease. Neurology 54:1753–1759

    Article  CAS  PubMed  Google Scholar 

  • Botsch H, Oepen G, Deuschl G et al (1987) SPECT studies with 99mTc-HMPAO in Huntington’s chorea patients. Röfo 147:666–668

    CAS  PubMed  Google Scholar 

  • Ciarmiello A, Cannella M, Lastoria S et al (2006) Brain white-matter volume loss and glucose hypometabolism precede the clinical symptoms of Huntington’s disease. J Nucl Med 47:215–222

    CAS  PubMed  Google Scholar 

  • Ciarmiello A, Giovacchini G, Orobello S et al (2012) (18)F-FDG PET uptake in the pre-Huntington disease caudate affects the time-to-onset independently of CAG expansion size. Eur J Nucl Med Mol Imaging 39:1030–1036

    Article  CAS  PubMed  Google Scholar 

  • Esmaeilzadeh M, Kullingsjo J, Ullman H et al (2011a) Regional cerebral glucose metabolism after pridopidine (ACR16) treatment in patients with Huntington disease. Clin Neuropharmacol 34:95–100

    Article  CAS  PubMed  Google Scholar 

  • Esmaeilzadeh M, Farde L, Karlsson P et al (2011b) Extrastriatal dopamine D(2) receptor binding in Huntington’s disease. Hum Brain Mapp 32:1626–1636

    Article  PubMed  Google Scholar 

  • Feigin A, Leenders KL, Moeller JR et al (2001) Metabolic network abnormalities in early Huntington’s disease: an [(18)F]FDG PET study. J Nucl Med 42:1591–1595

    CAS  PubMed  Google Scholar 

  • Feigin A, Tang C, Ma Y et al (2007) Thalamic metabolism and symptom onset in preclinical Huntington’s disease. Brain 130:2858–2867

    Article  CAS  PubMed  Google Scholar 

  • Furtado S, Sossi V, Hauser RA et al (2005) Positron emission tomography after fetal transplantation in Huntington’s disease. Ann Neurol 58:331–337

    Article  PubMed  Google Scholar 

  • Gallina P, Paganini M, Lombardini L et al (2010) Human striatal neuroblasts develop and build a striatal-like structure into the brain of Huntington’s disease patients after transplantation. Exp Neurol 222:30–41

    Article  PubMed  Google Scholar 

  • Gaura V, Bachoud-Levi AC, Ribeiro MJ et al (2004) Striatal neural grafting improves cortical metabolism in Huntington’s disease patients. Brain 127:65–72

    Article  PubMed  Google Scholar 

  • Ginovart N, Lundin A, Farde L et al (1997) PET study of the pre- and post-synaptic dopaminergic markers for the neurodegenerative process in Huntington’s disease. Brain 120(Pt 3):503–514

    Article  PubMed  Google Scholar 

  • Grafton ST, Mazziotta JC, Pahl JJ et al (1992) Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington’s disease. Arch Neurol 49:1161–1167

    Article  CAS  PubMed  Google Scholar 

  • Gusella JF, Wexler NS, Conneally PM et al (1983) A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 306:234–238

    Article  CAS  PubMed  Google Scholar 

  • Harris GJ, Aylward EH, Peyser CE et al (1996) Single photon emission computed tomographic blood flow and magnetic resonance volume imaging of basal ganglia in Huntington’s disease. Arch Neurol 53:316–324

    Article  CAS  PubMed  Google Scholar 

  • Hasselbalch SG, Oberg G, Sorensen SA et al (1992) Reduced regional cerebral blood flow in Huntington’s disease studied by SPECT. J Neurol Neurosurg Psychiatry 55:1018–1023

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hayden MR, Martin WR, Stoessl AJ et al (1986) Positron emission tomography in the early diagnosis of Huntington’s disease. Neurology 36:888–894

    Article  CAS  PubMed  Google Scholar 

  • Hayden MR, Hewitt J, Stoessl AJ et al (1987) The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington’s disease. Neurology 37:1441–1447

    Article  CAS  PubMed  Google Scholar 

  • Holthoff VA, Koeppe RA, Frey KA et al (1993) Positron emission tomography measures of benzodiazepine receptors in Huntington’s disease. Ann Neurol 34:76–81

    Article  CAS  PubMed  Google Scholar 

  • Huntington G (1872) On chorea. The Medical and Surgical Reporter 26:317–321

    Google Scholar 

  • Kremer B, Goldberg P, Andrew SE et al (1994) A worldwide study of the Huntington’s disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 330:1401–1406

    Article  CAS  PubMed  Google Scholar 

  • Kremer B, Clark CM, Almqvist EW et al (1999) Influence of lamotrigine on progression of early Huntington disease: a randomized clinical trial. Neurology 53:1000–1011

    Article  CAS  PubMed  Google Scholar 

  • Kuhl DE, Phelps ME, Markham CH et al (1982) Cerebral metabolism and atrophy in Huntington’s disease determined by 18FDG and computed tomographic scan. Ann Neurol 12:425–434

    Article  CAS  PubMed  Google Scholar 

  • Kunig G, Leenders KL, Sanchez-Pernaute R et al (2000) Benzodiazepine receptor binding in Huntington’s disease: [11C]flumazenil uptake measured using positron emission tomography. Ann Neurol 47:644–648

    Article  CAS  PubMed  Google Scholar 

  • Kuwert T, Lange HW, Langen KJ et al (1990) Cortical and subcortical glucose consumption measured by PET in patients with Huntington’s disease. Brain 113(Pt 5):1405–1423

    Article  PubMed  Google Scholar 

  • Kuwert T, Ganslandt T, Jansen P et al (1992) Influence of size of regions of interest on PET evaluation of caudate glucose consumption. J Comput Assist Tomogr 16:789–794

    Article  CAS  PubMed  Google Scholar 

  • Kuwert T, Lange HW, Boecker H et al (1993) Striatal glucose consumption in chorea-free subjects at risk of Huntington’s disease. J Neurol 241:31–36

    Article  CAS  PubMed  Google Scholar 

  • Landles C, Bates GP (2004) Huntingtin and the molecular pathogenesis of Huntington’s disease. Fourth in molecular medicine review series. EMBO Rep 5:958–963

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Landwehrmeyer GB, Dubois B, de Yebenes JG et al (2007) Riluzole in Huntington’s disease: a 3-year, randomized controlled study. Ann Neurol 62:262–272

    Article  CAS  PubMed  Google Scholar 

  • Lawrence AD, Weeks RA, Brooks DJ et al (1998) The relationship between striatal dopamine receptor binding and cognitive performance in Huntington’s disease. Brain 121(Pt 7):1343–1355

    Article  PubMed  Google Scholar 

  • Leslie WD, Greenberg CR, Abrams DN et al (1999) Clinical deficits in Huntington disease correlate with reduced striatal uptake on iodine-123 epidepride single-photon emission tomography. Eur J Nucl Med 26:1458–1464

    Article  CAS  PubMed  Google Scholar 

  • Mazziotta JC, Phelps ME, Pahl JJ et al (1987) Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington’s disease. N Engl J Med 316:357–362

    Article  CAS  PubMed  Google Scholar 

  • Muller-Gartner HW, Links JM, Prince JL et al (1992) Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects. J Cereb Blood Flow Metab 12:571–583

    Article  CAS  PubMed  Google Scholar 

  • Paulsen JS (2009) Functional imaging in Huntington’s disease. Exp Neurol 216:272–277

    Article  PubMed  Google Scholar 

  • Pavese N, Andrews TC, Brooks DJ et al (2003) Progressive striatal and cortical dopamine receptor dysfunction in Huntington’s disease: a PET study. Brain 126:1127–1135

    Article  PubMed  Google Scholar 

  • Pavese N, Gerhard A, Tai YF et al (2006) Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology 66:1638–1643

    Article  CAS  PubMed  Google Scholar 

  • Pavese N, Politis M, Tai YF et al (2010) Cortical dopamine dysfunction in symptomatic and premanifest Huntington’s disease gene carriers. Neurobiol Dis 37:356–361

    Article  CAS  PubMed  Google Scholar 

  • Pirker W, Asenbaum S, Wenger S et al (1997) Iodine-123-epidepride-SPECT: studies in Parkinson’s disease, multiple system atrophy and Huntington’s disease. J Nucl Med 38:1711–1717

    CAS  PubMed  Google Scholar 

  • Politis M, Pavese N, Tai YF et al (2008) Hypothalamic involvement in Huntington’s disease: an in vivo PET study. Brain 131:2860–2869

    Article  PubMed  Google Scholar 

  • Politis M, Pavese N, Tai YF et al (2011) Microglial activation in regions related to cognitive function predicts disease onset in Huntington’s disease: a multimodal imaging study. Hum Brain Mapp 32:258–270

    Article  PubMed  Google Scholar 

  • Reid IC, Besson JA, Best PV et al (1988) Imaging of cerebral blood flow markers in Huntington’s disease using single photon emission computed tomography. J Neurol Neurosurg Psychiatry 51:1264–1268

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rousset OG, Ma Y, Evans AC (1998) Correction for partial volume effects in PET: principle and validation. J Nucl Med 39:904–911

    CAS  PubMed  Google Scholar 

  • Sanchez-Pernaute R, Kunig G, del Barrio Alba A et al (2000) Bradykinesia in early Huntington’s disease. Neurology 54:119–125

    Article  CAS  PubMed  Google Scholar 

  • Schumacher JM, Hantraye P, Brownell AL et al (1992) A primate model of Huntington’s disease: functional neural transplantation and CT-guided stereotactic procedures. Cell Transplant 1:313–322

    CAS  PubMed  Google Scholar 

  • Sedvall G, Karlsson P, Lundin A et al (1994) Dopamine D1 receptor number–a sensitive PET marker for early brain degeneration in Huntington’s disease. Eur Arch Psychiatry Clin Neurosci 243:249–255

    Article  CAS  PubMed  Google Scholar 

  • Squitieri F, Gellera C, Cannella M et al (2003) Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course. Brain 126:946–955

    Article  PubMed  Google Scholar 

  • Squitieri F, Orobello S, Cannella M et al (2009) Riluzole protects Huntington disease patients from brain glucose hypometabolism and grey matter volume loss and increases production of neurotrophins. Eur J Nucl Med Mol Imaging 36:1113–1120

    Article  CAS  PubMed  Google Scholar 

  • Tabrizi SJ, Reilmann R, Roos RA et al (2012) Potential endpoints for clinical trials in premanifest and early Huntington’s disease in the TRACK-HD study: analysis of 24 month observational data. Lancet Neurol 11:42–53

    Article  PubMed  Google Scholar 

  • The Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983

    Article  Google Scholar 

  • van Oostrom JC, Maguire RP, Verschuuren-Bemelmans CC et al (2005) Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease. Neurology 65:941–943

    Article  PubMed  Google Scholar 

  • van Oostrom JC, Dekker M, Willemsen AT et al (2009) Changes in striatal dopamine D2 receptor binding in pre-clinical Huntington’s disease. Eur J Neurol 16:226–231

    Article  PubMed  Google Scholar 

  • Vonsattel JP, Myers RH, Stevens TJ et al (1985) Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol 44:559–577

    Article  CAS  PubMed  Google Scholar 

  • Vonsattel JP, Keller C, Cortes Ramirez EP (2011) Huntington’s disease - neuropathology. Handb Clin Neurol 100:83–100

    Article  PubMed  Google Scholar 

  • Walker FO (2007) Huntington’s disease. Lancet 369:218–228

    Article  CAS  PubMed  Google Scholar 

  • Young AB, Penney JB, Starosta-Rubinstein S et al (1986) PET scan investigations of Huntington’s disease: cerebral metabolic correlates of neurological features and functional decline. Ann Neurol 20:296–303

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. P. H. (Berry) Kremer .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kremer, H.P.H.(. (2014). PET in Huntington’s Disease. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Leenders, K. (eds) PET and SPECT in Neurology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54307-4_30

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-54307-4_30

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-54306-7

  • Online ISBN: 978-3-642-54307-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics