Safety and Efficacy of Radiosynoviorthesis: A Prospective Canadian Multicenter Study.

Radiosynoviorthesis is approved in several European countries and the United States to treat refractory synovitis in many inflammatory joint diseases, such as rheumatoid arthritis, spondyloarthropathies, and other arthritic joint diseases. No radiopharmaceuticals for radiosynoviorthesis are currently approved in Canada. The aim of this Health Canada-approved trial was to demonstrate the safety and efficacy of radiosynoviorthesis.

The effects of the β-adrenergic receptor antagonist bisoprolol administration on mirabegron-stimulated human brown adipose tissue thermogenesis.

Aim: Pharmacological stimulation of human brown adipose tissue (BAT) has been hindered by ineffective activation or undesirable off-target effects. Oral administration of the maximal allowable dose of mirabegron (200 mg), a β-adrenergic receptor (β-AR) agonist, has been effective in stimulating BAT thermogenesis and whole-body energy expenditure. However, this has been accompanied by undesirable cardiovascular effects.

High Tyrosol and Hydroxytyrosol Intake Reduces Arterial Inflammation and Atherosclerotic Lesion Microcalcification in Healthy Older Populations.

Aging is an important risk factor for cardiovascular diseases and convincing data have shown that chronic low-grade inflammation, which develops with advanced age, contributes significantly to cardiovascular risk. The present study aimed to use F-FDG/F-NaF-PET/CT imaging to, respectively, gauge arterial inflammation and microcalcification in a healthy elderly population and to assess the potential benefits of a tyrosol- and hydroxytyrosol-rich diet on these two markers of atherosclerotic plaque fragility. Eleven healthy participants (mean age 75 ± 5.

Non-calcified active atherosclerosis plaque detection with 18F-NaF and 18F-FDG PET/CT dynamic imaging.

Arterial inflammation is an indicator of atheromatous plaque vulnerability to detach and to obstruct blood vessels in the heart or in the brain thus causing heart attack or stroke. To date, it is difficult to predict the plaque vulnerability. This study was aimed to assess the behavior of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) uptake in the aorta and iliac arteries as a function of plaque density on CT images.

Intra-individual comparison of F-sodium fluoride PET-CT and Tc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial.

Background: Detection of skeletal metastases in patients with prostate cancer or breast cancer remains a major clinical challenge. We aimed to compare the diagnostic performance of Tc-methylene diphosphonate (Tc-MDP) single-photon emission CT (SPECT) and F-sodium fluoride (F-NaF) PET-CT for the detection of osseous metastases in patients with high-risk prostate or breast cancer.

Methods: MITNEC-A1 was a prospective, multicentre, single-cohort, phase 3 trial conducted in ten hospitals across Canada.

Ga-DOTATATE Prepared from Cyclotron-Produced Ga: An Integrated Solution from Cyclotron Vault to Safety Assessment and Diagnostic Efficacy in Neuroendocrine Cancer Patients.

Cyclotron production of Ga is a promising approach to supply Ga radiopharmaceuticals. To validate this capability, an integrated solution for a robust synthesis of Ga-DOTATATE prepared from cyclotron-produced Ga was achieved. A retrospective comparison analysis was performed on patients who underwent PET/CT imaging after injection of DOTATATE labeled with Ga produced by a cyclotron or eluted from a generator to demonstrate the clinical safety and diagnostic efficacy of the radiopharmaceutical as a routine standard-of-care diagnostic tool in the clinic.

Total Postprandial Hepatic Nonesterified and Dietary Fatty Acid Uptake Is Increased and Insufficiently Curbed by Adipose Tissue Fatty Acid Trapping in Prediabetes With Overweight.

Excessive lean tissue uptake of fatty acids (FAs) is important in the development of insulin resistance and may be caused by impaired dietary FA (DFA) storage and/or increased nonesterified FA (NEFA) flux from adipose tissue intracellular lipolysis. Cardiac and hepatic total postprandial FA uptake of NEFA+DFA has, however, never been reported in prediabetes with overweight. In this study, 20 individuals with impaired glucose tolerance (IGT) and 19 participants with normal glucose tolerance (NGT) and normal fasting glucose underwent postprandial studies with whole-body positron emission tomography/computed tomography (PET/CT) with oral [18F]fluoro-thia-heptadecanoic acid and dynamic PET/CT with intravenous [11C]palmitate.

DeepImageTranslator: A free, user-friendly graphical interface for image translation using deep-learning and its applications in 3D CT image analysis.

The advent of deep-learning has set new standards in an array of image translation applications. At present, the use of these methods often requires computer programming experience. Non-commercial programs with graphical interface usually do not allow users to fully customize their deep-learning pipeline.

Quantitative SPECT (QSPECT) at high count rates with contemporary SPECT/CT systems.

Background: Accurate QSPECT is crucial in dosimetry-based, personalized radiopharmaceutical therapy with Lu and other radionuclides. We compared the quantitative performance of three NaI(Tl)-crystal SPECT/CT systems equipped with low-energy high-resolution collimators from two vendors (Siemens Symbia T6; GE Discovery 670 and NM/CT 870 DR).

Methods: Using up to 14 GBq of Tc in planar mode, we determined the calibration factor and dead-time constant under the assumption that these systems have a paralyzable behaviour.

The Triple-Tracer strategy against Metastatic PrOstate cancer (3TMPO) study protocol.

Objective: To determine the prevalence of intra-patient inter-metastatic heterogeneity based on positron emission tomography (PET)/computed tomography (CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and to determine the prevalence of neuroendocrine disease in these patients and their eligibility for radioligand therapies (RLTs).

Patients And Methods: This multicentre observational prospective clinical study will include 100 patients with mCRPC from five Canadian academic centres. Patients with radiological or biochemical progression and harbouring at least three metastases by conventional imaging will be accrued.

F-4FMFES and F-FDG PET/CT in Estrogen Receptor-Positive Endometrial Carcinomas: Preliminary Report.

This article reports the preliminary results of a phase II clinical trial investigating the use of the estrogen receptor (ER)-targeting PET tracer 4-fluoro-11β-methoxy-16α-F-fluoroestradiol (F-4FMFES) and F-FDG PET in endometrial cancers. In parallel, noninvasive interventions were attempted to slow progression of F-4FMFES metabolites in the intestines to reduce abdominal background uptake. In an ongoing study, 25 patients who received prior pathologic confirmation of an ER-positive endometrial cancer or endometrial intraepithelial neoplasia agreed to participate in the ongoing clinical trial.

Increased postprandial nonesterified fatty acid efflux from adipose tissue in prediabetes is offset by enhanced dietary fatty acid adipose trapping.

The mechanism of increased postprandial nonesterified fatty acid (NEFA) appearance in the circulation in impaired glucose tolerance (IGT) is due to increased adipose tissue lipolysis but could also be contributed to by reduced adipose tissue (AT) dietary fatty acid (DFA) trapping and increased "spillover" into the circulation. Thirty-one subjects with IGT (14 women, 17 men) and 29 with normal glucose tolerance (NGT, 15 women, 14 men) underwent a meal test with oral and intravenous palmitate tracers and the oral [F]-fluoro-thia-heptadecanoic acid positron emission tomography method. Postprandial palmitate appearance (Ra) was higher in IGT versus NGT ( < 0.

Safety and therapeutic value of radiosynoviorthesis with yttrium-90: a Canadian single-centre experience.

Background: Yttrium-90 (90Y) is approved in several countries as a radiosynoviorthesis agent in the intra-articular treatment of synovitis, however, no such radiopharmaceuticals are approved in Canada. The aim of this Health Canada-approved study was to examine the safety and efficacy of 90Y synovectomy among patients with refractory synovitis.

Methods: We performed a subset analysis of a prospective, phase III, single-arm, pan-Canadian trial.

Focal Liver 18F-FDG Uptake in a Patient Who Underwent Thrombolysis for Brachiocephalic and Subclavian Thrombosis: A Potential Pitfall.

A 19-year-old woman presented with a primary mediastinal B-cell lymphoma invading the superior vena cava with associated thrombosis of the left brachiocephalic and subclavian vein. She underwent thrombolysis followed by chemotherapy. The midtreatment 18F-FDG PET/CT demonstrated important regression of the primary mediastinal B-cell lymphoma, but showed intense focal hepatic uptake in segment IV, without a corresponding lesion on ultrasonography, non-contrast-enhanced low-dose CT, and MRI.

Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation.

Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the β-adrenergic receptor (β-AR), the adrenergic receptor believed to mediate BAT thermogenesis, have historically performed poorly in human clinical trials. Here we report that, in contrast to rodents, human BAT thermogenesis is not mediated by the stimulation of β-AR.

Cross-Species Physiological Assessment of Brain Estrogen Receptor Expression Using F-FES and F-4FMFES PET Imaging.

Purpose: A retrospective analysis was performed of preclinical and clinical data acquired during the evaluation of the estrogen receptor (ER) PET tracer 4-fluoro-11β-methoxy-16α-[F]-fluoroestradiol (4FMFES) and its comparison with 16α-[F]-fluoroestradiol (FES) in mice, rats, and humans with a focus on the brain uptake.

Procedures: Breast cancer tumor-bearing female BALB/c mice from a previous study and female Sprague-Dawley rats (control and ovariectomized) were imaged by 4FMFES or FES-PET imaging. Immediately after, low-dose CT was performed in the same bed position.

A preclinical PET dual-tracer imaging protocol for ER and HER2 phenotyping in breast cancer xenografts.

Background: Nuclear medicine is on the constant search of precision radiopharmaceutical approaches to improve patient management. Although discordant expression of the estrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER2) in breast cancer is a known dilemma for appropriate patient management, traditional tumor sampling is often difficult or impractical. While 2-deoxy-2[F]fluoro-D-glucose (F-FDG)-positron emission tomography (PET) is an option to detect subclinical metastases, it does not provide phenotype information.

Fascicle- and Glucose-Specific Deterioration in White Matter Energy Supply in Alzheimer's Disease.

Background: White matter energy supply to oligodendrocytes and the axonal compartment is crucial for normal axonal function. Although gray matter glucose hypometabolism is extensively reported in Alzheimer's disease (AD), glucose and ketones, the brain's two main fuels, are rarely quantified in white matter in AD.

Objective: Using a dual-tracer PET method combined with a fascicle-specific diffusion MRI approach, robust to white matter hyper intensities and crossing fibers, we aimed to quantify both glucose and ketone metabolism in specific white matter fascicles associated with mild cognitive impairment (MCI; n = 51) and AD (n = 13) compared to cognitively healthy age-matched controls (Controls; n = 14).

Bariatric Surgery Rapidly Decreases Cardiac Dietary Fatty Acid Partitioning and Hepatic Insulin Resistance Through Increased Intra-abdominal Adipose Tissue Storage and Reduced Spillover in Type 2 Diabetes.

Reduced storage of dietary fatty acids (DFAs) in abdominal adipose tissues with enhanced cardiac partitioning has been shown in subjects with type 2 diabetes (T2D) and prediabetes. We measured DFA metabolism and organ partitioning using positron emission tomography with oral and intravenous long-chain fatty acid and glucose tracers during a standard liquid meal in 12 obese subjects with T2D before and 8-12 days after bariatric surgery (sleeve gastrectomy or sleeve gastrectomy and biliopancreatic diversion with duodenal switch). Bariatric surgery reduced cardiac DFA uptake from a median (standard uptake value [SUV]) 1.

Seven-day overfeeding enhances adipose tissue dietary fatty acid storage and decreases myocardial and skeletal muscle dietary fatty acid partitioning in healthy subjects.

Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV) function is associated with insulin resistance in prediabetes. We hypothesized that enhanced myocardial DFA partitioning and reduced LV function might be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high-saturated fat (~11%energy), and simple carbohydrates (~54%energy) diet (HIGHCAL) versus an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8%energy) and carbohydrates (~50%energy). Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL versus ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14()-[F]fluoro-6-thia-heptadecanoic acid and [C]acetate positron emission tomography methods at the end of both interventions.

A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment.

Introduction: Unlike for glucose, uptake of the brain's main alternative fuel, ketones, remains normal in mild cognitive impairment (MCI). Ketogenic medium chain triglycerides (kMCTs) could improve cognition in MCI by providing the brain with more fuel.

Methods: Fifty-two subjects with MCI were blindly randomized to 30 g/day of kMCT or matching placebo.

Links Between Metabolic and Structural Changes in the Brain of Cognitively Normal Older Adults: A 4-Year Longitudinal Follow-Up.

We aimed to longitudinally assess the relationship between changing brain energy metabolism (glucose and acetoacetate) and cognition during healthy aging. Participants aged 71 ± 5 year underwent cognitive evaluation and quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) scans at baseline ( = 25) and two ( = 25) and four ( = 16) years later. During the follow-up, the rate constant for brain extraction of glucose (K) declined by 6%-12% mainly in the temporo-parietal lobes and cingulate gyri ( ≤ 0.