This title appears in the Scientific Report :
2012
Cerebral Nicotinic Acetylcholine Receptors (nAChRs) In EarlyAlzheimer’s Disease (AD) Assessed With The New Radioligand [18F]Flubatine and PET
Cerebral Nicotinic Acetylcholine Receptors (nAChRs) In EarlyAlzheimer’s Disease (AD) Assessed With The New Radioligand [18F]Flubatine and PET
Objectives: 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 significa...
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Personal Name(s): | Sabri, O (Corresponding author) (Corresponding author) |
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Wilke, S / Graef, S / Lengler, U / Schoenknecht, P / Gertz, H / Becker, G / Luthardt, J / Patt, M / Hesse, S / Barthel, H / Wagenknecht, Gudrun / Hoepping, A / Hegerl, U / Brust, P | |
Contributing Institute: |
Zentralinstitut für Elektronik; ZEL Zentralinstitut für Elektronik; ZEA-2 |
Imprint: |
2012
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Conference: | Annual Congress of the European Association of Nuclear Medicine, Milan (Italy), 2012-10-27 - 2012-10-31 |
Document Type: |
Conference Presentation |
Research Program: |
NorChloro-Fluoro HomoEpiBatidin (NCFHEB) ein potentieller Positronen-Emission Tomographie-(PET) Marker der frühen Alzheimer-Demenz Pathophysiological Mechanisms of Neurological and Psychiatric Diseases |
Publikationsportal JuSER |
Objectives: 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. |