α4β2 nicotinic receptor status in Alzheimer's disease using 123I-5IA-85380 single-photon-emission computed tomography

O'Brien, J. T.; Colloby, S. J.; Pakrasi, S.; Perry, E. K.; Pimlott, S. L.; Wyper, D. J.; McKeith, I. G.; Williams, E. D.
April 2007
Journal of Neurology, Neurosurgery & Psychiatry;Apr2007, Vol. 78 Issue 4, p356
Academic Journal
Background: Loss of the α4β2 nicotinic receptor subtype is found at autopsy in Alzheimer's disease. Objective: To investigate in vivo changes in this receptor using single-photon-emission CT (SPECT) with 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380), a novel nicotinic acetylcholine receptor ligand which binds predominantly to the α4β2 receptor. Methods: 32 non-smoking subjects (16 with Alzheimer's disease and 16 normal elderly controls) underwent 123I-5IA-85380 and perfusion (99mTc-hexamethylenepropyleneamine oxime (HMPAO)) SPECT scanning. Region of interest analysis was performed with cerebellar normalisation. Results: Significant bilateral reductions in nicotinic receptor binding were identified in frontal (left, p=0.004; right, p=0.002), striatal (left, p=0.004; right, p=0.003), right medial temporal (p=0.04) and pons (p<0.001) in patients with AD compared to controls. There were no significant correlations with clinical or cognitive measures. The pattern of nicotinic binding significantly differed from that of perfusion in both patients with AD and controls. Both 123I-5IA-85380 and 99mTc-HMPAO SPECT imaging demonstrated similar diagnostic performance in correctly classifying controls and patients with AD. Conclusion: Using 123I-5IA-85380 SPECT we found changes consistent with significant reductions in the nicotinic α4β2 receptor in cortical and striatal brain regions. This method could facilitate diagnosis and may be useful for monitoring progression of the disease and response to treatment in patients with AD and related diseases.


Related Articles

  • Reproducibility of [123I]PE2I binding to dopamine transporters with SPECT. Ziebell, Morten; Thomsen, Gerda; Knudsen, Gitte M.; de Nijs, Robin; Svarer, Claus; Wagner, Aase; Pinborg, Lars H. // European Journal of Nuclear Medicine & Molecular Imaging;Jan2007, Vol. 34 Issue 1, p101 

    The iodinated cocaine derivative [123I]PE2I is a new selective ligand for in vivo studies of the dopamine transporter (DAT) with SPECT. Recently, a bolus/infusion (B/I) protocol for [123I]PE2I measurements of DAT density was established [Pinborg LH et al. J Nucl Med 2005;46:1119–271]. The...

  • Risk stratification among diabetic patients undergoing stress myocardial perfusion imaging. Ghatak, Abhijit; Padala, Santosh; Katten, Deborah; Polk, Donna; Heller, Gary // Journal of Nuclear Cardiology;Aug2013, Vol. 20 Issue 4, p529 

    Background: Previous studies have suggested that diabetic patients undergoing single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) are at greater risk for cardiac events than non-diabetic patients with both normal and abnormal imaging results. However, the impact...

  • The clinical value of single photon emission computed tomography myocardial perfusion imaging in cardiac risk stratification of very elderly patients (≥80 years) with suspected coronary artery disease. Nair, Sanjeev; Ahlberg, Alan; Mathur, Shishir; Katten, Deborah; Polk, Donna; Heller, Gary // Journal of Nuclear Cardiology;Apr2012, Vol. 19 Issue 2, p244 

    Background: The role of single photon emission computed tomography myocardial perfusion imaging (SPECT MPI) in cardiac evaluation of the very elderly patients is unclear. We investigated the clinical value of SPECT MPI in very elderly patients (≥80 years) with suspected coronary artery...

  • Nicotinic receptor structure emerging slowly. Sixma, Titia K. // Nature Neuroscience;Aug2007, Vol. 10 Issue 8, p937 

    The article discusses a concerning a high-resolution crystal structure of nicotinic receptors. The high resolution of the new structure reveals new features which are described in the study. The new structure is only a monomer and does not form a functional ligand-binding site. The analysis of...

  • Coronary artery ectasia causing ischemia. Husmann, Lars; Herzog, Bernhard; Burkhard, Nina; Valenta, Ines; Weber, Klaus; Kaufmann, Philipp // European Journal of Nuclear Medicine & Molecular Imaging;Nov2008, Vol. 35 Issue 11, p2142 

    The article reports a case of coronary artery ectasia that is causing ischemia. 99mTc-Tetrofosmin single-photon emission computed tomography (SPECT) images reveal ectasia in the left anterior descending, the circumflex, and the right coronary artery, but without coronary artery stenosis. A...

  • Cerebral perfusion (HMPAO-SPECT) in patients with depression with cognitive impairment versus those with mild cognitive impairment and dementia of Alzheimer’s type: a semiquantitative and automated evaluation. Staffen, W.; Bergmann, J.; Schönauer, U.; Zauner, H.; Kronbichler, M.; Golaszewski, S.; Ladurner, G. // European Journal of Nuclear Medicine & Molecular Imaging;May2009, Vol. 36 Issue 5, p801 

    Comparative evaluation of regional brain perfusion measured by HMPAO-SPECT of patients with mild cognitive impairment (MCI), dementia of Alzheimer’s type (DAT) and depression with cognitive impairment (DCI). A total of 736 patients were investigated because of suspected cognitive...

  • Partial volume effect correction in SPECT for striatal uptake measurements in patients with neurodegenerative diseases: impact upon patient classification. Soret, Marine; Koulibaly, Pierre; Darcourt, Jacques; Buvat, Irène // European Journal of Nuclear Medicine & Molecular Imaging;Sep2006, Vol. 33 Issue 9, p1062 

    Purpose: In single-photon emission computed tomography (SPECT) of the dopaminergic system, measurements of striatal uptake are useful for diagnosis and patient follow-up but are strongly biased by the partial volume effect (PVE). We studied whether PVE correction might improve patient...

  • Are Brain SPECT Data and Neuropsychological Disturbances Correlated in Patients With Alzheimer Disease and Vascular Dementia? CEYLAN GÜNAY, Emel; Özgür YALIN, Osman; ÖZGE, Aynur; ERDOĞAN, Alihan; KIRAL, Kahraman; SUNGUR, Mehmet Ali; TELLİOĞLU, Burcu; ÖZCAN KARA, Pelin; KANIK, Arzu // Journal of Neurological Sciences;2014, Vol. 31 Issue 1, p47 

    Background: The clinical identification and the role of imaging in the differential diagnosis of dementia is challenging. The aim of this study is to investigate the characteristics and correlation of neurophsychological test battery and the semi-quantitative brain SPECT imaging in Alzheimer's...

  • Preclinical properties and human in vivo assessment of 123I-ABC577 as a novel SPECT agent for imaging amyloid-β. Yoshifumi Maya; Yuki Okumura; Ryohei Kobayashi; Takako Onishi; Yoshinari Shoyama; Olivier Barret; David Alagille; Danna Jennings; Kenneth Marek; John Seibyl; Gilles Tamagnan; Akihiro Tanaka; Yoshifumi Shirakami; Maya, Yoshifumi; Okumura, Yuki; Kobayashi, Ryohei; Onishi, Takako; Shoyama, Yoshinari; Barret, Olivier; Alagille, David // Brain: A Journal of Neurology;Jan2016, Vol. 139 Issue 1, p193 

    Non-invasive imaging of amyloid-β in the brain, a hallmark of Alzheimer's disease, may support earlier and more accurate diagnosis of the disease. In this study, we assessed the novel single photon emission computed tomography tracer (123)I-ABC577 as a potential imaging biomarker for...


Read the Article


Sign out of this library

Other Topics