Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf
Cerebral alpha4beta2 nicotinic acetylcholine receptors (nAChRs) in early Alzheimer disease (AD) assessed with the new PET tracer (-)-[18F]-norchloro-fluoro-homoepibatidine (NCFHEB)
Sabri, O.; Wilke, S.; Graef, S.; Schoenknecht, P.; Becker, G.; Patt, M.; Wagenknecht, G.; Hoepping, A.; Hegerl, U.; Brust, P.
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
SNM 58th Annual Meeting, 04.-08.06.2011, San Antonio, Texas, USA
Abstract in refereed journal
Journal of Nuclear Medicine 52(2011), 1267