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Objectives This is a first-in-human study of the PET radiotracer 11C-LSN3172176 for the muscarinic acetylcholine receptor subtype 1 (M1). The objectives of this study were to determine the appropriate kinetic model to quantify the tracer's binding to M1 receptors, and the reliability of the chosen quantification method. Methods Six healthy subjects completed the test-retest protocol and five healthy subjects completed the baseline-scopolamine blocking protocol. Multiple modeling methods were applied to calculate volume of distribution (VT) and binding potentials (BPND) in various brain regions. The reference region was selected from the blocking study. The occupancy plot was applied to compute receptor occupancy by scopolamine and non-displaceable distribution volume (VND). Results Tracer uptake was highest in the striatum, followed by neocortical regions and white matter, and lowest in the cerebellum. Regional time-activity curves were fitted well by all models. The two-tissue compartment (2TC) model fits weels are appropriate methods for quantitative analysis of 11C-LSN3172176 imaging data. 11C-LSN3172176 displayed excellent test-retest reproducibility and is a highly promising ligand to quantify M1 receptors in the human brain.The aims were to decrease 177Lu-SPECT (single-photon emission computed tomography) acquisition time by reducing the number of projections and to circumvent image degradation by adding deep learning-generated synthesized projections. Methods We constructed a deep convolutional U-structured network for generating synthetic intermediate projections (CUSIP). The number of SPECT investigations was 352 for training, 37 for validation, and 15 for testing. The input was every fourth projection of 120 acquired SPECT projections, i.e., 30 projections. The output was 30 synthetic intermediate projections (SIPs) per CUSIP. SPECT images were reconstructed with 120 or 30 projections, or 120 projections where 90 SIPs were generated from the 30 projections (30-120SIP); using 3 CUSIPs. The reconstructions were performed with two ordered subset expectation maximization (OSEM) algorithms attenuation-corrected (AC)-OSEM, and attenuation, scatter, and collimator response-corrected (ASCC)-OSEM. Image quality of SIPs and SPECT imagding values were 2/60 for the 30-120SIP and 120 projection sets. Image quality did not differ significantly between the 30-120SIP and 120 projection reconstructions. The kidney activity concentration was similar between the different projection sets, excepting a minor reduction of 2.5% for the ASCC-OSEM 30-120SIP. Conclusion Adopting synthetic intermediate projections for sparsely acquired projections considerably recovers image quality and could allow reduced SPECT acquisition time in clinical dosimetry protocols.Rationale Pheochromocytomas and paragangliomas are a rare tumor entity originating from adreno-medullary chromaffin cells in the adrenal medulla or in sympathetic, paravertebral ganglia outside the medulla. Especially small lesions are difficult to detect by conventional CT or MR imaging and even by SPECT imaging with currently available radiotracers (e.g. MIBG). The novel PET-radiotracer F-18-flubrobenguane could change the diagnostic paradigm in suspected pheochromocytomas and paragangliomas due to its homology to MIBG and the general advantages of PET-imaging. Aim of this retrospective analysis was to evaluate F-18-flubrobenguane in pheochromocytomas and paragangliomas and to investigate the biodistribution in patients. Methods 24 Patients with suspected pheochromocytoma and paraganglioma underwent PET/CT or PET/MRI at 63±24 min p.i. after injection of 256±33 MBq F-18-flubrobenguane. SUVmean and SUVmax values of organs were measured with spherical volume-of-interests. Threshold segmented volume-of-interest 23 (23/47, 49%) lesions smaller than 1 cm were found on hybrid imaging only. Conclusion Our preliminary data suggest F-18-flubrobenguane PET as a new effective staging tool in patients with suspected pheochromocytoma and paraganglioma. Major advantages are the fast acquisition and high spatial resolution of PET imaging and intense uptake in tumor lesions facilitating lesion detection. Further studies are warranted to define its role particularly in comparison to standard diagnostic procedures such as MRI or I-123-MIBG SPECT/CT.Rationale Myocardial infarction (MI) is one of the leading causes of death worldwide and inflammation is central to the tissue response and patient outcomes. The 18kDa translocator protein (TSPO) has been utilized in positron emission tomography (PET) as an inflammatory biomarker. The aims of this study were to 1) screen novel, fluorinated, TSPO radiotracers for susceptibility to the rs6971 genetic polymorphism using in vitro competition binding assays in human brain and heart, 2) assess whether the in vivo characteristics of our lead radiotracer, 18F-LW223, are suitable for clinical translation and 3) validate whether 18F-LW223 can detect macrophage driven inflammation in a rat myocardial infarction model. Methods Fifty-one human brain and twenty-nine human heart tissue samples were screened for the rs6971 polymorphism. Competition binding assays were conducted with 3H-PK11195 and the following ligands PK11195, PBR28 and our novel compounds (AB5186 and LW223). Naive rats and mice were used for in vivo PET ki8 (macrophage marker) resulted in the same pattern seen with in vivo BPTC analysis. Selleck Levofloxacin Conclusion18F-LW223 is not susceptible to the rs6971 genetic polymorphism in in vitro assays, has favorable in vivo characteristics and is able to accurately map macrophage driven inflammation following MI.Previous histopathological and animal studies have shown axonal impairment and loss of connectivity of the nigrostriatal pathway in Parkinson disease (PD). However, there are conflicting reports from in vivo human studies. 11C-dihydrotetrabenazine (11C-DTBZ) is a vesicular monoamine type 2 transporter PET ligand that allows assessment of nigrostriatal presynaptic dopaminergic terminal integrity. Correlational tractography based on diffusion magnetic resonance imaging can incorporate ligand-specific information provided by 11C-DTBZ PET into the fiber tracking process. The purpose of this study was to assess the in vivo association between the integrity of the nigrostriatal tract (defined by correlational tractography) and the degree of striatal dopaminergic denervation based on 11C-DTBZ PET. Methods The study involved 30 subjects with mild to moderate PD (23 males; 7 females; mean age 66 ± 6.2 years, disease duration 6.4 ± 4.0 years; Hoehn and Yahr stage 2.1 ±0.6; MDS-revised UPDRS (I -III) total score 43.4 ± 17.

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