PT  - JOURNAL ARTICLE
AU  - Sabri, Osama
AU  - Wilke, S.
AU  - Graef, Susanne
AU  - Schoenknecht, P.
AU  - Becker, Georg
AU  - Patt, Marianne
AU  - Wagenknecht, Gudrun
AU  - Hoepping, A.
AU  - Hegerl, U.
AU  - Brust, Peter
TI  - Cerebral alpha4beta2 nicotinic acetylcholine receptors (nAChRs) in early Alzheimer disease (AD) assessed with the new PET tracer (-)-[18F]-norchloro-fluoro-homoepibatidine (NCFHEB)
DP  - 2011 May 01
TA  - Journal of Nuclear Medicine
PG  - 1267--1267
VI  - 52
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/52/supplement_1/1267.short
4100  - http://jnm.snmjournals.org/content/52/supplement_1/1267.full
SO  - J Nucl Med2011 May 01; 52
AB  - 1267 Objectives Using 2-[18F]F-A85380 (2FA) PET we showed significant nAChRs declines in early AD (EJNMMI 2010). However, this tracer is not well suited in routine use for early AD-diagnosis because of slow kinetics, acquisition times up to 7 hours, and limited nAChR selectivity. Thus, we developed the new tracer NCFHEB (Synapse 2008). This is the worldwide first ongoing human NCFHEB-PET study. Methods 6 mild AD-patients (age 76.7±5.9, MMSE 23.8±3.0) and 5 age-matched healthy controls (HC, age 71.1±5.3, MMSE 28.4±1.1) underwent NCFHEB-PET (370 MBq, 3D, ECAT Exact HR+) from 0-270 min p.i. Kinetic modeling was applied to tissue-activity curves in 29 individual MRI-defined ROIs (1 tissue compartment model: 1TCM, arterial input-function). Total distribution volume (DV) and binding potential (BP, reference: corpus callosum) were calculated. Results NCFHEB image quality was clearly superior to 2FA, and a 20 min scan already adequate for visual analysis. PET data acquired over only 90 min were sufficient to estimate all kinetic parameters precisely (1TCM) indicating a fast receptor binding kinetic (much faster than for 2FA). DVs in HCs increased as expected with receptor density: Corpus callosum (DV: 4.8±0.3), post cingulate (8.9±0.6), temporal (9.0±0.4), thalamus (24.3±2.9). AD-patients showed extensive BP reductions in frontal, parietal, temporal, cingulate cortices, and hippocampus compared to HCs (all p<0.05). Conclusions Significant shorter acquisition times and superior image quality indicate that NCFHEB is a more valuable tracer than 2FA to image human nAChRs. Early AD-patients show significant nAChRs declines in AD-affected brain ROIs. NCFHEB-PET has a great potential to be tested as a biomarker for early AD-diagnosis