Visualizing the in vivo activity of monoamine oxidase B (MAO-B) is a valuable tool in the ongoing investigation of astrogliosis in neurodegeneration. Existing strategies for imaging changes in MAO enzyme expression or activity have utilized the irreversible suicide inhibitors or high-affinity reversibly binding inhibitors as positron emission tomography (PET) ligands. As an alternative approach, we developed 4-methyl-7-[(1-[C]methyl-1,2,3,6-tetrahydropyridin-4-yl)oxy]-2 H-chromen-2-one ([C]Cou) as a metabolic trapping agent for MAO-B. Trapping of [C]Cou in rhesus monkey brain demonstrated MAO-B selectivity. In this work, we have attempted to improve on the in vivo pharmacokinetics of [C]Cou by using the deuterium kinetic isotope effect (KIE) to slow the MAO-B-mediated oxidation step and thus reduce the rate of trapping in brain tissues. However, in vitro assays of enzyme kinetics and in vivo PET imaging of pharmacokinetics in primate brain showed no effects of deuterium substitution on the tetrahydropyridine ring of [C]Cou. The results are possibly due to masking of the KIE by a second step in the overall metabolism of the new imaging agent.

BackgroundWe recently upgraded our [18F]fludeoxyglucose (FDG) production capabilities with the goal of futureproofing our FDG clinical supply, expanding the number of batches of FDG we can manufacture each day, and improving patient throughput in our nuclear medicine clinic. In this paper we report upgrade of the synthesis modules to the GE FASTLab 2 platform (Phase 1) and cyclotron updates (Phase 2) from both practical and regulatory perspectives. We summarize our experience manufacturing FDG on the FASTLab 2 module with a high-yielding self-shielded niobium (Nb) fluorine-18 target.ResultsFollowing installation of Nb targets for production of fluorine-18, a 55 μA beam for 22 min generated 1330 ± 153 mCi of [18F]fluoride. Using these cyclotron beam parameters in combination with the FASTLab 2, activity yields (AY) of FDG were 957 ± 102 mCi at EOS, corresponding to 72% non-corrected AY (n = 235). Our workflow, inventory management and regulatory compliance have been greatly simplified following the synthesis module and cyclotron upgrades, and patient wait times for FDG PET have been cut in half at our nuclear medicine clinic.ConclusionsThe combination of FASTlab 2 and self-shielded Nb fluorine-18 targets have improved our yield of FDG, and enabled reliable and repeatable manufacture of the radiotracer for clinical use.

ImportanceAtherosclerotic cardiovascular disease (ASCVD) continues to be highly prevalent in the US. The 2013 American College of Cardiology and American Heart Association (ACC/AHA) treatment guidelines reevaluated evidence-based practices for reduction of ASCVD in men and women from high-quality randomized trials and meta-analyses recommending the use of statin therapy, aspirin prescription, and lifestyle counseling for adults with ASCVD. Population trends in secondary prevention strategies for patients with ASCVD among primary care settings is currently lacking, limiting ability to evaluate impact of guideline implementation.ObjectiveTo examine temporal and sociodemographic trends in secondary prevention strategies in patients with ASCVD between 2006 and 2016 in a nationally representative, ambulatory care database.Design, Setting, and ParticipantsThis cross-sectional study analyzed data from the National Ambulatory Medical Care Survey (NAMCS), which is an annual survey conducted to represent the national US population and contains information on ambulatory office-based patient visits, including medical conditions, services provided, and demographic characteristics. Participants were adults aged 21 years and older with prevalent ASCVD identified via International Classification of Disease codes between 2006 and 2016. Data were extracted and analyzed in March 2021.Main Outcomes and MeasuresData were separated by calendar year pre-2013 (2006 to 2013) and post-2013 (2014 to 2016). Outcomes included statin therapy, aspirin prescription, and lifestyle counseling (eg, nutrition, exercise, weight reduction) service provided at clinic visits.ResultsThere were 11 033 visits for adults with ASCVD, representing a weighted total of 275.3 million visits nationwide; 40.7% (112.1 million [weighted]) were women, 9.2% (25.4 million [weighted]) were Hispanic, 9.9% (19.0 million [weighted]) were non-Hispanic Black, 90.1% (172.7 million [weighted]) were non-Hispanic White, and 40.6% (112.1 million [weighted]) were from cardiology clinics. Of 11 033 patient visits, 5507 patients (49.9%) were prescribed statin therapy, 5165 patients (46.8%) were using aspirin, 2233 patients (20.2%) received lifestyle counseling. Statin therapy increased from 9.3 million individuals (45.3%) in 2006 to 14.9 million individuals (46.5%) in 2016, and aspirin prescriptions increased from 8.5 million individuals (41.3%) in 2006 to 15.2 individuals (47.5%) in 2016. Women were less likely than men to receive medications for secondary prevention: among women, 48.8 million (43.3%) received statins (vs 85.9 million men [52.7%]), 44.7 million (39.8%) received aspirin (vs 79.1 million men [48.5%]), and 25.7 million (22.9%) received lifestyle counseling services (vs 37.5 million men [23.0%]).Conclusions and RelevanceThese findings suggest only modest increases in statin and aspirin prescription since 2006; however, lifestyle counseling use decreased in recent years. Women and Black patients continued to be less likely to receive secondary prevention ASCVD treatment. Adherence to guideline-directed secondary prevention recommendations remained low (less than 50%) in patients with ASCVD, especially with regards to lifestyle counseling, suggesting the need for more implementation research.

BACKGROUND Symptom descriptions in outpatients with COVID-19 are limited to cross-sectional surveys and longitudinal follow-up of long term symptoms has not been reported. Symptom duration is important for patient and provider knowledge in managing outpatient COVID-19. OBJECTIVE Describe the presence of symptoms at long term follow-up of patients managed in an outpatient telemedicine program for acute COVID-19. METHODS Chart review of clinical notes for acute COVID-19 and long term follow-up calls. Descriptive analysis were conducted using Wilcoxon rank-sum for continuous variables and chi-square or Fisher’s Exact as appropriate for categorical variables. RESULTS Minor symptoms were reported by 55 patients (34.8%) and 7 (4.4%) reported major ongoing symptoms at follow-up call. Factors associated with prolonged symptoms include older age, provider reported higher symptom severity at intake visit, and BMI >30. Symptoms which persisted include shortness of breath on exertion, wheeze, nausea, and joint pain. CONCLUSIONS Persistence of symptoms after acute COVID-19 in outpatients is common. Risk factors may help predict which patients are more likely to have prolonged symptoms.

The radiotracers [11C]­COU and [11C]­PHXY are potential PET imaging agents for in vivo studies of monoamine oxidases (MAOs), as previously shown in rodent and primate brain. One-pot, automated methods for the radiosynthesis of [11C]­PHXY and [11C]­COU were developed to provide reliable and improved radiochemical yields. Although derived from the structure of the neurotoxin MPTP, COU did not exhibit in vivo neurotoxicity to dopaminergic nerve terminals in the mouse brain as assayed by losses of VMAT2 radioligand binding. PET imaging studies in rats demonstrated that both [11C]­COU and [11C]­PHXY exhibit retention in cardiac tissues that can be blocked by pretreatment with the MAO inhibitors deprenyl (MAO-B) and pargyline (MAO-A and -B). In addition to prior neuroimaging applications, [11C]­COU and [11C]­PHXY are thus also of interest for studies of MAO enzymatic activity and imaging of sympathetic nerve density in heart.