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000131849 005__ 20250129092401.0
000131849 0247_ $$2DOI$$a10.1007/s00259-012-2221-x
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000131849 1001_ $$0P:(DE-HGF)0$$aSabri, O$$b0$$eCorresponding author
000131849 1112_ $$aAnnual Congress of the European Association of Nuclear Medicine$$cMilan$$d2012-10-27 - 2012-10-31$$gEANM2012$$wItaly
000131849 245__ $$aCerebral Nicotinic Acetylcholine Receptors (nAChRs) In EarlyAlzheimer’s Disease (AD) Assessed With The New Radioligand [18F]Flubatine and PET
000131849 260__ $$aHeidelberg [u.a.]$$bSpringer-Verl.$$c2012
000131849 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1360757515_26002
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000131849 3367_ $$2BibTeX$$aARTICLE
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000131849 500__ $$3POF3_Assignment on 2016-02-29
000131849 520__ $$aObjectives: There is evidence from post‐mortem studies that the loss of nAChRs, in particular of the alpha4beta2‐nAChR, which is obviously most severely reduced at the onset of AD, is a major contributor to the cognitive deterioration in AD. Accordingly, using 2‐[18F]F‐A85380 PET we showed significant declines in alpha4beta2‐nAChRs in early AD‐patients (Sabri et al. 2008; Kendziorra et al. 2010). However, this tracer was not well suited as a biomarker in a routine clinical set‐up for early AD‐diagnosis because of unfavourable properties (especially long acquisition times up to 7 hours). We, therefore, developed the new radiotracer (‐)‐ [18F]NCFHEB (denominated as [18F]Flubatine) with significantly improved brain uptake and also better nAChR affinity and selectivity (Brust et al. 2008). Here, we present the results of the worldwide first ongoing [18F]Flubatine‐PET study in humans.   Methods: 19 mild AD‐patients (NINCDS‐ADRDA, age 74.5±6.2, MMSE 23.7±2.7) and 20 age‐matched healthy controls (HC, age 70.6±4.6, MMSE 28.5±0.8) underwent [18F]Flubatine‐PET (370 MBq, 3D‐acquisition, ECAT Exact HR+, 4 scans, 0‐270 min p.i., motion correction with SPM2). All were nonsmokers and naïve for central acting medication. Kinetic modeling was applied to the VOI‐based tissueactivity curves generated for 29 brain regions. Total distribution volume (DV) and binding potential (BP, reference region: corpus callosum) were used to characterize specific binding. Additionally, parametric images of DV were computed (Logan plot).   Results: Image quality of [18F]Flubatine scans was clearly superior to 2‐[18F]FA85380, and a 20 minutes scan already adequate for visual analysis. PET data acquired over only 90 minutes were sufficient to estimate all kinetic parameters of all VOIs with 1‐tissue compartment model. Thirty‐minute scans were already sufficient for modelling of all cortical VOIs. Tracer distribution was similar to known alpha4beta2‐nAChR distribution and DVs in HCs increase as expected with receptor density with the lowest DV in the corpus callosum (5.64±0,87) and highest in the thalamus (24.67±3.91). The AD‐patients showed significant BP reductions in distinct cortical regions (p<0.05) compared to HCs.   Conclusions: Due to significant faster kinetics and shorter acquisition time enabling full kinetic modeling within 90 minutes, and superior image quality [18F]Flubatine appears to be a much more suitable tracer than 2‐[18F]F‐A85380 to image alpha4beta2‐nAChRs in humans. In keeping with its diagnostic properties, early AD‐patients show declines of alpha4beta2‐nAChRs in distinct cortical regions typically affected by AD‐pathology. These results indicate that [18F]Flubatine‐PET could have a great potential to be tested as a biomarker for early AD‐diagnosis.
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000131849 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$$x1
000131849 7001_ $$0P:(DE-HGF)0$$aWilke, S$$b1
000131849 7001_ $$0P:(DE-HGF)0$$aGraef, S$$b2
000131849 7001_ $$0P:(DE-HGF)0$$aLengler, U$$b3
000131849 7001_ $$0P:(DE-HGF)0$$aSchoenknecht, P$$b4
000131849 7001_ $$0P:(DE-HGF)0$$aGertz, H$$b5
000131849 7001_ $$0P:(DE-HGF)0$$aBecker, G$$b6
000131849 7001_ $$0P:(DE-HGF)0$$aLuthardt, J$$b7
000131849 7001_ $$0P:(DE-HGF)0$$aPatt, M$$b8
000131849 7001_ $$0P:(DE-HGF)0$$aHesse, S$$b9
000131849 7001_ $$0P:(DE-HGF)0$$aBarthel, H$$b10
000131849 7001_ $$0P:(DE-Juel1)133954$$aWagenknecht, Gudrun$$b11
000131849 7001_ $$0P:(DE-HGF)0$$aHoepping, A$$b12
000131849 7001_ $$0P:(DE-HGF)0$$aHegerl, U$$b13
000131849 7001_ $$0P:(DE-HGF)0$$aBrust, P$$b14
000131849 773__ $$0PERI:(DE-600)2098375-X$$a10.1007/s00259-012-2221-x$$nSuppl 2$$pS221 (OP347)$$tEuropean journal of nuclear medicine and molecular imaging$$v39$$x1432-105X
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000131849 9141_ $$y2012
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