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| Home > Publications database > Comparison of (-)-[18F]-Flubatine and 2-[18F]FA-85380 Binding to Nicotinic alpha4beta2 Acetylcholine Receptors in Human Brains. |
| Home > Publications database > Comparison of (-)-[18F]-Flubatine and 2-[18F]FA-85380 Binding to Nicotinic alpha4beta2 Acetylcholine Receptors in Human Brains. |
| Journal Article | FZJ-2014-00445 |
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2013
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Abstract: Aim: Nicotinic α4β2* acetylcholine receptors (nAChR) are an important target for diagnostic neuroimaging because of their involvement in Alzheimer's disease, Parkinson's disease, tobacco and alcohol addiction. 2-[18F]FA-85380 (2-FA) has been used extensively for PET imaging of α4β2* receptors but is limited as biomarker by its unfavourable slow kinetic. The newly developed radiotracer (-)-[18F]-Flubatine (Flubatine) shows a significantly improved brain uptake, receptor affinity and selectivity (1). Here we estimated the compartmental parameters of both tracers by full kinetic modeling and compared them. Materials and Methods: After intravenous administration of ~370 MBq radiotracer PET brain imaging was performed in 20 healthy controls with Flubatine (age 70.6±4.6, scan duration 90 min) and in 7 healthy controls with 2-FA (age 60.7±9.0, scan duration 420 min) using an ECAT EXACT HR+ system. PET frames were motion corrected with SPM2 and kinetic modeling using a 1-tissue compartment model (1TCM) with arterial input-function was applied to the volume of interest (VOI) based tissue time-activity curves (TACs) generated for 29 brain regions (anatomically defined via MRI co-registration). The model-based receptor parameter used was the total distribution volume VT (ml/cm3), tracer uptake was measured by K1 (ml/cm3/min) and tracer tissue clearance by k2 (1/min). Results: For both tracers TACs of all 29 brain regions could be described appropriately with the 1TCM and all kinetic parameters could be reliably estimated from the PET data. Regional VT increased as expected with regional nAChR density. Parameters of Flubatine in characteristic regions with very low, medium and high receptor density were: Corpus callosum (K1= 0.18±0.04, k2= 0.032±0.004, VT= 5.68±1.01), Frontal cortex (K1= 0.37±0.04, k2= 0.040±0.003, VT= 9.18±0.59), Thalamus (K1= 0.48±0.06, k2= 0.020±0.003, VT= 25.03±3.33). The respective parameters of 2-FA were: Corpus callosum (K1= 0.063±0.009, k2= 0.014±0.003, VT= 4.45±0.65), Frontal cortex (K1= 0.099±0.013, k2= 0.018±0.001, VT= 5.42±0.56), Thalamus (K1= 0.13±0.019, k2= 0.010±0.001, VT= 13.06±2.62). Conclusions: Flubatine is superior to 2-FA in tracer uptake velocity (characterized by K1), velocity of washout (characterized by k2) and in the amount of measured specific binding (characterized by VT-target - VT-reference). It shows a threefold higher uptake rate constant K1 and a twofold higher washout rate constant k2, providing the rational for much shorter scan durations in case of Flubatine. These results are in good agreement with our former findings in an animal (pig) model (1). Reference: 1. P. Brust, ..O. Sabri: In vivo measurement of nicotinic acetylcholine receptors with [18F]Norchloro-Fluoro-Homoepibatidine (Flubatine). Synapse 2008;62:205-218.
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