This title appears in the Scientific Report :
2012
PET Quantification Of 18F-Flubatine Binding To Nicotinic alpha4beta2 acetylcholine receptors in Human Brains
PET Quantification Of 18F-Flubatine Binding To Nicotinic alpha4beta2 acetylcholine receptors in Human Brains
Objectives: Nicotinic alpha4beta2 acetylcholine receptors (nAChR) are an important target for diagnostic neuroimaging because of their involvement in Alzheimer's disease (AD) and Parkinson's disease. Using 2-[18F]F-A85380 PET a significant decline in alpha4beta2-nAChRs in early AD-patients...
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Personal Name(s): | Becker, G (Corresponding author) |
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Wilke, S / Schönknecht, P / Patt, M / Luthardt, J / Hesse, S / Wagenknecht, Gudrun / Höpping, A / Brust, P / Sabri, O | |
Contributing Institute: |
Zentralinstitut für Elektronik; ZEL Zentralinstitut für Elektronik; ZEA-2 |
Imprint: |
2012
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Conference: | The 9th International Symposium on Functional Neuroreceptor Mapping of the Living Brain, Baltimore (USA), 2012-08-09 - 2012-08-11 |
Document Type: |
Poster |
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: Nicotinic alpha4beta2 acetylcholine receptors (nAChR) are an important target for diagnostic neuroimaging because of their involvement in Alzheimer's disease (AD) and Parkinson's disease. Using 2-[18F]F-A85380 PET a significant decline in alpha4beta2-nAChRs in early AD-patients which correlated to loss of cognitive function was shown (1, 2). However, this tracer is not suited for use as biomarker for early AD-diagnosis in a routine clinical set-up because of its unfavourable slow kinetics. Here we used the new radiotracer (-)-[18F]-Flubatine (formerly (-)-[18F]-NCFHEB) with significantly improved brain uptake, receptor affinity and selectivity (3). nAChR-parameters were determined by full kinetic modeling and the validity of the practically useful tissue ratio and tissue-to-plasma ratio as receptor parameters was evaluated. Methods: After intravenous administration of ~370 MBq (-)-[18F]-Flubatine, the PET brain imaging was performed in 20 healthy controls (age 70.6±4.6) using an ECAT EXACT HR+ system in 3D-acquisition mode. 23 frames were acquired from 0-90 min post injection and motion corrected with SPM2. Kinetic modeling using a 1-tissue compartment model (1TCM) with arterial input-function was applied to the volume of interest (VOI) based tissue-activity curves (TACs) generated for 29 brain regions (anatomically defined via MRI co-registration). Model-based receptor parameters used were the total distribution volume (VT) and the distribution volume ratio (DVR) (reference: posterior corpus callosum). In addition the standardized uptake value ratio (SUVR) (50-70 min) as approximation of the DVR and the tissue-to-plasma concentration ratio (TTPR) (70-90 min) as approximation of VT were used as non model-based receptor parameters. Results: TACs of all 29 regions could be described adequately with the 1TCM and all kinetic parameters could be reliably estimated from 90 min PET data. VT increased as expected with receptor density. Corpus callosum (VT: 5.68±1.01), frontal cortex (9.18±0.59), parietal cortex (9.10±0.61), pons (11.10±0.86), thalamus (25.03±3.33). Mean TTPR values in frontal and parietal cortices were 2% higher than the corresponding VT values but 7% lower in the thalamus. There was a strong linear correlation between the two sets of TTPR and VT values (r2 = 0.98, p < 10-4) (Fig. 1A). As VT, DVR increased with receptor density. Frontal cortex (DVR: 1.66±0.27), parietal cortex (1.64±0.27), pons (2.01±0.35), thalamus (4.52±0.87). Mean SUVR values in frontal and parietal cortices were almost identical to mean DVR values (difference <0.1%) but ~15 % lower in the thalamus. Accordingly there was a strong linear correlation between the SUVR and DVR values (r2 = 0.97, p < 10-4) (Fig. 1B). Conclusions: For (-)-[18F]-Flubatine the receptor parameters TTPR and SUVR in cortical regions are in excellent agreement with corresponding parameters computed by full kinetic modeling. For unbiased estimates of TTPR and SUVR in the thalamus the use of a bolus/infusion scheme for tracer application should be considered. References: 1. O. Sabri, ..P. Brust: Acetylcholine receptors in dementia and mild cognitive impairment. Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 1): 30-45. 2. K. Kendziorra, ..O. Sabri: Decreased cerebral a4ß2 nicotinic acetylcholine receptors in living patients with mild cognitive impairment and Alzheimer's disease assessed with positron emission tomography. Eur J Nucl Med Mol Imaging 2010; 38: 515-525. 3. P. Brust, ..O. Sabri: In-vivo measurement of nicotinic acetylcholine receptors with [18 F]norchloro-fluoro-homoepibatidine (NCFHEB). Synapse 2008; 62: 205-218. Linear regression analysis. (A) Tissue-to-plasma concentration ratio (TTPR) and total distribution volume (VT). (B) Standardized uptake value ratio (SUVR) and distribution volume ratio (DVR). |