Results of a Prospective Trial to Compare Ga-DOTA-TATE with SiPM-Based PET/CT vs. Conventional PET/CT in Patients with Neuroendocrine Tumors.

We prospectively enrolled patients with neuroendocrine tumors (NETs). They underwent a single Ga-DOTA-TATE injection followed by dual imaging and were randomly scanned using first either the conventional or the silicon photomultiplier (SiPM) positron emission tomography/computed tomography (PET/CT), followed by imaging using the other system. A total of 94 patients, 44 men and 50 women, between 35 and 91 years old (mean ± SD: 63 ± 11.

Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease.

Background: Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer's disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [F]BCPP-EF.

Usefulness of semi-automatic harmonization strategy of standardized uptake values for multicenter PET studies.

This study assessed the possibility of semi-automatic harmonization of standardized uptake values (SUVs) in multicenter studies. Phantom data were acquired using 16 PET/CT scanners (including 3 PET/CT scanners with a silicon photomultiplier detector). PET images obtained using 30-min/bed scans for optimum harmonization filter calculations and using 90-180-s/bed scans for SUV validation under clinical conditions were obtained.

Tofacitinib in the Treatment of Moderate-to-Severe Rheumatoid Arthritis in China: A Cost-Effectiveness Analysis Based on a Mapping Algorithm Derived from a Chinese Population.

Introduction: To estimate the cost-effectiveness of tofacitinib for patients with moderate-to-severe rheumatoid arthritis (RA) who failed conventional synthetic disease-modifying antirheumatic drugs from the Chinese healthcare system perspective.

Methods: An individual patient simulation model was used to estimate the lifetime cost and effectiveness. The comparator sequence commenced with etanercept, followed by rituximab-tocilizumab- non-biologic therapy.

Development of F-Labeled Radiotracers for PET Imaging of the Adenosine A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation.

The adenosine A receptor (AR) represents a potential therapeutic target for neurodegenerative diseases. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor changes of receptor density and/or occupancy during the AR-tailored therapy, we designed a library of fluorinated analogs based on a recently published lead compound (). Among those, the highly affine 4-fluorobenzyl derivate (; (AR) = 5.

Multiparametric magnetic resonance imaging and positron emission tomography findings in neurodegenerative diseases: Current status and future directions.

Neurodegenerative diseases (NDDs) are characterized by progressive neuronal loss, leading to dementia and movement disorders. NDDs broadly include Alzheimer's disease, frontotemporal lobar degeneration, parkinsonian syndromes, and prion diseases. There is an ever-increasing prevalence of mild cognitive impairment and dementia, with an accompanying immense economic impact, prompting efforts aimed at early identification and effective interventions.

Cerebral blood flow measurements with O-water PET using a non-invasive machine-learning-derived arterial input function.

Cerebral blood flow (CBF) can be measured with dynamic positron emission tomography (PET) of O-labeled water by using tracer kinetic modelling. However, for quantification of regional CBF, an arterial input function (AIF), obtained from arterial blood sampling, is required. In this work we evaluated a novel, non-invasive approach for input function prediction based on machine learning (MLIF), against AIF for CBF PET measurements in human subjects.

Beta-catenin activation and immunotherapy resistance in hepatocellular carcinoma: mechanisms and biomarkers.

Mutations involving CTNNB1, the gene encoding beta-catenin, and other molecular alterations that affect the Wnt/beta-catenin signaling pathway are exceptionally common in hepatocellular carcinoma. Several of these alterations have also been associated with scarcity of immune cells in the tumor microenvironment and poor clinical response to immune checkpoint inhibitor therapy. In light of these associations, tumor biomarkers of beta-catenin status could have the potential to serve as clinical predictors of immunotherapy outcome.

The standardized uptake value calculated from In-ibritumomab tiuxetan single-photon emission computed tomography/computed tomography is a useful predictor of the clinical response in patients treated by Y- ibritumomab tiuxetan therapy.

Y-Ibritumomab tiuxetan (IT) therapy is a radioimmunotherapy for indolent B-cell lymphoma. Several predictors of insufficient therapeutic effects have been reported. We performed a retrospective study at a single institute to investigate whether In SPECT/CT can predict the therapeutic effects and grade of cytopenia due to Y-IT therapy.

Synthesis and Biological Evaluation of a Novel F-Labeled Radiotracer for PET Imaging of the Adenosine A Receptor.

The adenosine A receptor (AR) has emerged as a potential non-dopaminergic target for the treatment of Parkinson's disease and, thus, the non-invasive imaging with positron emission tomography (PET) is of utmost importance to monitor the receptor expression and occupancy during an AR-tailored therapy. Aiming at the development of a PET radiotracer, we herein report the design of a series of novel fluorinated analogs (-) based on the structure of the AR antagonist , and the preclinical evaluation of [F]. Autoradiography proved AR-specific in vitro binding of [F] to striatum of mouse and pig brain.

Machine learning derived input-function in a dynamic F-FDG PET study of mice.

Tracer kinetic modelling, based on dynamic F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used to quantify glucose metabolism in humans and animals. Knowledge of the arterial input-function (AIF) is required for such measurements. Our aim was to explore two non-invasive machine learning-based models, for AIF prediction in a small-animal dynamic FDG PET study.

Cost-effectiveness analysis of adding ramucirumab to the first-line erlotinib treatment for untreated EGFR-mutated metastatic non-small cell lung cancer in China.

Objective: To investigate the cost-effectiveness of ramucirumab plus erlotinib compared with placebo plus erlotinib in the first-line setting for patients with EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) from the Chinese healthcare system perspective.

Design: A Markov model consisting of three health states using clinical survival data from the RELAY phase III randomised clinical trial, a lifetime horizon for costs and quality-adjusted life-years (QALYs) was constructed to analyse the cost-effectiveness of ramucirumab plus erlotinib. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of the model.

Neural correlates of standing imagery and execution in Parkinsonian patients: The relevance to striatal dopamine dysfunction.

It has been reported that the cerebellar vermis is equally involved in both motor imagery about axial movement and the actual execution of postural balance in healthy human subjects, but this finding is yet to be explored in Parkinson's disease (PD). We therefore investigated the neuronal responses during observation of standing posture, imagination of standing and the assumption of an upright posture in ten drug-naïve PD patients using positron emission tomography (PET) with [15O]H2O and evaluated dopamine dysfunction by measuring the level of dopamine transporter binding of [11C]CFT. Within-group statistical parametric mapping (SPM) analysis showed similar cerebellar activation during imagination of standing and its real execution between the PD and control groups (12 healthy subjects); i.

Perfluoroalkyl acids potentiate glutamate excitotoxicity in rat cerebellar granule neurons.

Perfluoroalkyl acids (PFAAs) are persistent man-made chemicals, ubiquitous in nature and present in human samples. Although restrictions are being introduced, they are still used in industrial processes as well as in consumer products. PFAAs cross the blood-brain-barrier and have been observed to induce adverse neurobehavioural effects in humans and animals as well as adverse effects in neuronal in vitro studies.

Texture Feature Comparison Between Step-and-Shoot and Continuous-Bed-Motion F-FDG PET.

Our objective was to investigate the differences in texture features between step-and-shoot (SS) and continuous-bed-motion (CBM) imaging in phantom and clinical studies. A National Electrical Manufacturers Association body phantom was filled with F-FDG solution at a sphere-to-background ratio of 4:1. SS and CBM were performed using the same acquisition duration, and the data were reconstructed using 3-dimensional ordered-subset expectation maximization with time-of-flight algorithms.

Discovery of a Lead Brain-Penetrating Gonadotropin-Releasing Hormone Receptor Antagonist with Saturable Binding in Brain.

We report the synthesis, radiosynthesis and biological characterisation of two gonadotropin-releasing hormone receptor (GnRH-R) antagonists with nanomolar binding affinity. A small library of GnRH-R antagonists was synthesised in 20-67 % overall yield with the aim of identifying a high-affinity antagonist capable of crossing the blood-brain barrier. Binding affinity to rat GnRH-R was determined by autoradiography in competitive-binding studies against [ I]buserelin, and inhibition constants were calculated by using the Cheng-Prusoff equation.

Coronary Flow Capacity to Identify Stenosis Associated With Coronary Flow Improvement After Revascularization: A Combined Analysis From DEFINE FLOW and IDEAL.

Background Coronary flow capacity (CFC), which is a categorical assessment based on the combination of hyperemic coronary flow and coronary flow reserve (CFR), has been introduced as a comprehensive assessment of the coronary circulation to overcome the limitations of CFR alone. The aim of this study was to quantify coronary flow changes after percutaneous coronary intervention in relation to the classification of CFC and the current physiological cutoff values of fractional flow reserve, instantaneous wave-free ratio, and CFR. Methods and Results Using the combined data set from DEFINE FLOW (Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect -Combined Pressure and Doppler FLOW Velocity Measurements) and IDEAL (Iberian-Dutch-English), a total of 133 vessels that underwent intracoronary Doppler flow measurement before and after percutaneous coronary intervention were analyzed.

Accuracy of metabolic volume and total glycolysis among six threshold-based target segmentation algorithms.

Objective: This study aimed to evaluate the accuracy of six threshold-based segmentation methods with different target-to-background ratios (TBR), images with different voxel sizes and image noise, in measuring metabolic volume (MV) and total glycolysis (TG).

Methods: A standard body phantom consisting of six spheres (inner diameters of 37, 28, 22, 17, 13, and 10 mm) was filled with F-FDG solution. The background radioactivity level was 2.

In vivo imaging of dopamine D1 receptor and activated microglia in attention-deficit/hyperactivity disorder: a positron emission tomography study.

Alterations in the cortical dopamine system and microglial activation have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), one of neurodevelopmental disorders that can be conventionally treated with a dopamine enhancer (methylphenidate) albeit unsatisfactorily. Here, we investigated the contributions of the dopamine D1 receptor (D1R) and activated microglia and their interactions to the clinical severities in ADHD individuals using positron emission tomography (PET). Twenty-four psychotropic-naïve ADHD individuals and 24 age- and sex-matched typically developing (TD) subjects underwent PET measurements with [C]SCH23390 for the D1R and [C](R)PK11195 for activated microglia as well as assessments of clinical symptoms and cognitive functions.

Sigma-1 Receptor Positron Emission Tomography: A New Molecular Imaging Approach Using ()-(-)-[F]Fluspidine in Glioblastoma.

Glioblastoma multiforme (GBM) is the most devastating primary brain tumour characterised by infiltrative growth and resistance to therapies. According to recent research, the sigma-1 receptor (sig1R), an endoplasmic reticulum chaperone protein, is involved in signaling pathways assumed to control the proliferation of cancer cells and thus could serve as candidate for molecular characterisation of GBM. To test this hypothesis, we used the clinically applied sig1R-ligand ()-(-)-[F]fluspidine in imaging studies in an orthotopic mouse model of GBM (U87-MG) as well as in human GBM tissue.

PET Imaging of the Adenosine A Receptor in the Rotenone-Based Mouse Model of Parkinson's Disease with [F]FESCH Synthesized by a Simplified Two-Step One-Pot Radiolabeling Strategy.

The adenosine A receptor (AR) is regarded as a particularly appropriate target for non-dopaminergic treatment of Parkinson's disease (PD). An increased AR availability has been found in the human striatum at early stages of PD and in patients with PD and dyskinesias. The aim of this small animal positron emission tomography/magnetic resonance (PET/MR) imaging study was to investigate whether rotenone-treated mice reflect the aspect of striatal AR upregulation in PD.

In vivo mitochondrial and glycolytic impairments in patients with Alzheimer disease.

Objective: In vivo glycolysis-related glucose metabolism and electron transport chain-related mitochondrial activity may be different regionally in the brains of patients with Alzheimer disease (AD). To test this hypothesis regarding AD pathophysiology, we measured the availability of mitochondrial complex-I (MC-I) with the novel PET probe [F]2-tert- butyl-4-chloro-5-2H- pyridazin-3-one ([F]BCPP-EF), which binds to MC-I, and compared [F]BCPP-EF uptake with F-fluorodeoxyglucose ([F]FDG) uptake in the living AD brain.

Methods: First, the total distribution volume (V) of [F]BCPP-EF from 10 normal controls (NCs) was quantified using arterial blood samples and then tested to observe whether V could substitute for the standard uptake value relative to the global count (SUVRg).

Distal Evaluation of Functional performance with Intravascular sensors to assess the Narrowing Effect-combined pressure and Doppler FLOW velocity measurements (DEFINE-FLOW) trial: Rationale and trial design.

Background: It remains uncertain if invasive coronary physiology beyond fractional flow reserve (FFR) can refine lesion selection for revascularization or provide additional prognostic value. Coronary flow reserve (CFR) equals the ratio of hyperemic to baseline flow velocity and has a wealth of invasive and noninvasive data supporting its validity. Because of fundamental physiologic relationships, binary classification of FFR and CFR disagrees in approximately 30%-40% of cases.

DIAGNOSTIC IMAGING AND IONIZING RADIATION EXPOSURE IN A LEVEL 1 TRAUMA CENTRE POPULATION MET WITH TRAUMA TEAM ACTIVATION: A ONE-YEAR PATIENT RECORD AUDIT.

This audit describes ionizing and non-ionizing diagnostic imaging at a regional trauma centre. All 144 patients (males 79.2%, median age 31 years) met with trauma team activation from 1 January 2015 to 31 December 2015 were included.