Search

Introduction: We aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3)., Methods: 17 genetically-confirmed SCA3 patients and 16 controls underwent structural MRI and static resting-state [ 18 F]‑Fluoro‑deoxyglucose Positron Emission Tomography (FDG-PET) imaging. A SCA3-related pattern (SCA3-RP) was identified using a multivariate method (scaled subprofile model and principal component analysis (SSM PCA)). Participants were evaluated with the Scale for Assessment and Rating of Ataxia (SARA) and with neuropsychological examination including tests for language, executive dysfunction, memory, and information processing speed. The relationships between SCA3-RP expression and clinical scores were explored. Voxel based morphology (VBM) was applied on MRI-T1 images to assess possible correlations between FDG reduction and grey matter atrophy., Results: The SCA3-RP disclosed relative hypometabolism of the cerebellum, caudate nucleus and posterior parietal cortex, and relatively increased metabolism in somatosensory areas and the limbic system. This topography, which was not explained by regional atrophy, correlated significantly with ataxia (SARA) scores (ρ = 0.72; P  = 0.001). SCA3 patients showed significant deficits in executive function and information processing speed, but only letter fluency correlated with SCA3-RP expression (ρ = 0.51; P  = 0.04, uncorrected for multiple comparisons)., Conclusion: The SCA3 metabolic profile reflects network-level alterations which are primarily associated with the motor features of the disease. Striatum decreases additional to cerebellar hypometabolism underscores an intrinsic extrapyramidal involvement in SCA3. Cerebellar-posterior parietal hypometabolism together with anterior parietal (sensory) cortex hypermetabolism may reflect a shift from impaired feedforward to compensatory feedback processing in higher-order motor control. The demonstrated SCA3-RP provides basic insight in cerebral network changes in this disease.

The estrogen receptor (ER) is a target for endocrine therapy in breast cancer patients. Individual quantification of ERα and ERβ expression, rather than total ER levels, might enable better prediction of the response to treatment. We recently developed the tracer 2- 18 F-fluoro-6-(6-hydroxynaphthalen-2-yl)pyridin-3-ol ( 18 F-FHNP) for assessment of ERβ levels with PET. In the current study, we investigated several pharmacokinetic analysis methods to quantify changes in ERβ availability with 18 F-FHNP PET. Methods: Male nude rats were subcutaneously inoculated in the shoulder with ERα/ERβ-expressing SKOV3 human ovarian cancer cells. Two weeks after tumor inoculation, a dynamic 18 F-FHNP PET scan with arterial blood sampling was acquired from rats treated with vehicle or various concentrations of estradiol (nonspecific ER agonist) or genistein (ERβ-selective agonist). Different pharmacokinetic models were applied to quantify ERβ availability in the tumor. Results: Irreversible-uptake compartmental models fitted the kinetics of 18 F-FHNP uptake better than reversible models. The irreversible 3-tissue-compartment model, which included both the parent and the metabolite input function, gave results comparable to those of the irreversible 2-tissue-compartment model with only a parent input function, indicating that radioactive metabolites contributed little to the tumor uptake. Patlak graphical analysis gave metabolic rates ( K i , the irreversible uptake rate constant) comparable to compartment modeling. The K i values correlated well with ERβ expression but not with ERα, confirming that K i is a suitable parameter to quantify ERβ expression. SUVs at 60 min after tracer injection also correlated ( r 2 = 0.47; P = 0.04) with ERβ expression. A reduction in 18 F-FHNP tumor uptake and K i values was observed in the presence of estradiol or genistein. Conclusion: 18 F-FHNP PET enables assessment of ERβ availability in tumor-bearing rats. The most suitable parameter to quantify ERβ expression is the K i However, a simplified static imaging protocol for determining the SUVs can be applied to assess ERβ levels., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

In recent years, there have been multiple advances in positron emission tomography/computed tomography (PET/CT) that improve cancer imaging. The present generation of PET/CT scanners introduces new hardware, software, and acquisition methods. This review describes these new developments, which include time-of-flight (TOF), point-spread-function (PSF), maximum-a-posteriori (MAP) based reconstruction, smaller voxels, respiratory gating, metal artefact reduction, and administration of quadratic weight-dependent 18 F-fluorodeoxyglucose (FDG) activity. Also, hardware developments such as continuous bed motion (CBM), (digital) solid-state photodetectors and combined PET and magnetic resonance (MR) systems are explained. These novel techniques have a significant impact on cancer imaging, as they result in better image quality, improved small lesion detectability, and more accurate quantification of radiopharmaceutical uptake. This influences cancer diagnosis and staging, as well as therapy response monitoring and radiotherapy planning. Finally, the possible impact of these developments on the European Association of Nuclear Medicine (EANM) guidelines and EANM Research Ltd. (EARL) accreditation for FDG-PET/CT tumor imaging is discussed.