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000131879 1001_ $$0P:(DE-HGF)0$$aSabri, O$$b0$$eCorresponding author
000131879 1112_ $$a50. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin$$cBremen$$d2012-04-25 - 2012-04-28$$gDGN2012$$wGermany
000131879 245__ $$aFirst in man study with the new radioligand F-18-Flubatine to image alpha4beta2 cerebral nicotinic acetylcholine receptors (nAChRs) in early Alzheimer’s disease (AD) with PET
000131879 260__ $$aStuttgart$$bSchattauer$$c2012
000131879 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1360765077_27738
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000131879 500__ $$3POF3_Assignment on 2016-02-29
000131879 520__ $$aZiel/Aim: Using F-18-A85380 (2FA) PET we recently demonstrated significant cerebral nAChR declines in early AD which correlated significantly with the loss of cognitive function (1-2). However, 2FA is not well suited in clinical routine use because of slow kinetics, acquisition times up to 7 hours, and limited nAChR selectivity. Thus, we developed the new tracer F-18-Flubatine, an epibatidine derivative without toxicity in humans formerly named as F-18-NCFHEB (3) and report here on the worldwide first human Flubatine-PET results.  Methodik/Methods: 16 mild AD patients (NINCDS-ADRDA, age 74.4±6.6, MMSE 23.7±2.8) and 11 age-matched healthy controls (HCs, MMSE 28.5±0.9), all nonsmokers and nave for central acting medication, underwent Flubatine- PET (370 MBq, 3D-acquisition, ECAT Exact HR+). Dynamic 0-270min p.i.  scans were acquired and corrected for motion (SPM2). Kinetic modeling was applied to 29 brain VOI-based tissue-activity curves (VOIs defined on individual MRI) using a one-tissue compartment model with measured arterial input function. Total distribution volume (DV) and binding potential (BP, reference region: corpus callosum) were used to characterize specific binding.  Ergebnisse/Results: Image quality of Flubatine scans was clearly superior to 2FA, and a 20 minutes scan already adequate for visual analysis. All 29 regions were well described with one-tissue compartment. PET data acquired over only 90 minutes were sufficient to estimate all kinetic parameters precisely indicating a fast receptor binding kinetic (much faster than for 2FA). DVs in HCs increase as expected with receptor density: Corpus callosum (DV: 4.81±0.32), posterior cingulate (8.92±0.66), temporal (9.03±0.44), pons (11.00±1.19), thalamus (24.32±2.96). The AD patients showed extensive BP reductions in frontal, parietal, temporal, anterior and posterior cingulate cortices, caudate, and midbrain (all p<0.05) compared to HCs. There was significant correlation between nAChR reductions and cognitive declines in posterior cingulate, parietal, and temporal cortices, as well as in pons and cerebellum (p<0.05, all r> 0.41).  Schlussfolgerungen/Conclusions: Due to the significant shorter acquisition time and superior image quality Flubatine appears to be a much more valuable tracer than 2FA to image nAChRs in humans. Early AD patients show significant declines of nAChRs in brain regions typically affected by AD pathology which correlate well with the corresponding cognitive declines. These results indicate that Flubatine-PET has a great potential as a biomarker for early AD diagnosis.  Literatur/References: (1) Sabri et al. Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 1): 30-45 (2) Kendziorra et al., Eur J Nucl Med Mol Imaging 2011; 38: 515-525 (3) Brust et al. Synapse 2008; 62: 205-218 This trial is granted by the German Federal Ministry of Education and Research (BMBF-Nr. 01EZ0820)
000131879 536__ $$0G:(DE-HGF)POF2-333$$a333 - Pathophysiological Mechanisms of Neurological and Psychiatric Diseases (POF2-333)$$cPOF2-333$$fPOF II$$x0
000131879 536__ $$0G:(DE-Juel1)BMBF-01EZ0822$$aBMBF-01EZ0822 - NorChloro-Fluoro HomoEpiBatidin (NCFHEB)  ein potentieller Positronen-Emission Tomographie-(PET) Marker der frühen Alzheimer-Demenz (BMBF-01EZ0822)$$cBMBF-01EZ0822$$x1
000131879 7001_ $$0P:(DE-HGF)0$$aWilke, S$$b1
000131879 7001_ $$0P:(DE-HGF)0$$aGräf, S$$b2
000131879 7001_ $$0P:(DE-HGF)0$$aLengler, U$$b3
000131879 7001_ $$0P:(DE-HGF)0$$aGertz, H$$b4
000131879 7001_ $$0P:(DE-HGF)0$$aSchönknecht, P$$b5
000131879 7001_ $$0P:(DE-HGF)0$$aHabermann, B$$b6
000131879 7001_ $$0P:(DE-HGF)0$$aBecker, G$$b7
000131879 7001_ $$0P:(DE-HGF)0$$aLuthardt, J$$b8
000131879 7001_ $$0P:(DE-HGF)0$$aPatt, M$$b9
000131879 7001_ $$0P:(DE-HGF)0$$aKendziorra, K$$b10
000131879 7001_ $$0P:(DE-HGF)0$$aMeyer, P$$b11
000131879 7001_ $$0P:(DE-HGF)0$$aHesse, S$$b12
000131879 7001_ $$0P:(DE-HGF)0$$aBarthel, H$$b13
000131879 7001_ $$0P:(DE-HGF)0$$aSteinbach, J$$b14
000131879 7001_ $$0P:(DE-Juel1)133954$$aWagenknecht, Gudrun$$b15
000131879 7001_ $$0P:(DE-HGF)0$$aHöpping, A$$b16
000131879 7001_ $$0P:(DE-HGF)0$$aHegerl, U$$b17
000131879 7001_ $$0P:(DE-HGF)0$$aBrust, P$$b18
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