Optimization of the radiosynthesis of [18F]MEFWAY for imaging brain serotonin 1A receptors by using the GE TracerLab FXFN‐Pro module

The aim of this study was to develop a highly reliable radiofluorination method for the preparation of N‐{2‐[4‐(2‐methoxyphenyl)piperazinyl]ethyl}‐N‐(2‐pyridyl)‐N‐(4‐¹⁸F‐fluoromethylcyclohexane)carboxamide ([¹⁸F]Mefway) by using a fully automated system. The optimal condition is composed of two parts. The extraction system of the trapped F‐18 in the anion exchange resin (i.e., quaternary methylamine cartridge) is a complex of Kryptofix 2.2.2. (K222, 4 mg/0.9 mL methanol) and K₂CO₃ (1 mg/0.1 mL H₂O). After removing the solvents, the trans‐tosylated Mefway precursor (1 mg/0.5 mL acetonitrile) was reacted with dried K222‐K[¹⁸F] at 100°C for 5 min. After purification and formulation, [¹⁸F]Mefway was obtained with 38 ± 2.4% (decay corrected, n = 34) radiochemical yield, a total synthesis time of 52 ± 3.4 min, specific activity was 120.6 ± 8.7 GBq/µmol at the end of synthesis and a radiochemical purity of 99%. According to the quality control tests, formulated [¹⁸F]Mefway is suitable to apply parenteral clinical application.     

Wall shear stress measured by phase contrast cardiovascular magnetic resonance in children and adolescents with pulmonary arterial hypertension

Background

Pulmonary arterial hypertension (PAH) is a devastating disease with significant morbidity and mortality. At the macroscopic level, disease progression is observed as a complex interplay between mean pulmonary artery pressure, pulmonary vascular resistance, pulmonary vascular stiffness, arterial size, and flow. Wall shear stress (WSS) is known to mediate or be dependent on a number of these factors. Given that WSS is known to promote architectural vessel remodeling, it is imperative that the changes of this factor be quantified in the presence of PAH.

Methods

In this study, we analyzed phase contrast imaging of the right pulmonary artery derived from cardiovascular magnetic resonance to quantify the local, temporal and circumferentially averaged WSS of a PAH population and a pediatric control population. In addition, information about flow and relative area change were derived.

Results

Although the normotensive and PAH shear waveform exhibited a WSS profile which is uniform in magnitude and direction along the vessel circumference at systole, time-averaged WSS (2.2 ± 1.6 vs. 6.6 ± 3.4 dynes/cm², P = 0.018) and systolic WSS (8.2 ± 5.0 v. 20.0 ± 9.1 dynes/cm², P = 0.018) was significantly depressed in the PAH population as compared to the controls. BSA-indexed PA diameter was significantly larger in the PAH population (1.5 ± 0.4 vs. 0.7 ± 0.1 cm/m², P = 0.003).

Conclusions

In the presence of preserved flow rates through a large PAH pulmonary artery, WSS is significantly decreased. This may have implications for proximal pulmonary artery remodeling and cellular function in the progression of PAH.     

It’s a marathon not a sprint: the need for long-term monitoring of myocardial dysfunction in COVID-19

The International Journal of Cardiovascular Imaging -     

External beam radiation for localized periocular amyloidosis: a case series

Purpose: To evaluate the effectiveness of low dose external beam radiation therapy to halt progression of localized periocular light chain (AL) amyloidosis, a clonal plasma cell disorder.

Methods: This is a retrospective review of patients referred to a tertiary care center for external beam radiation treatment of biopsy proven localized periocular light chain amyloidosis. The primary outcome measure was clinical disease stability at one year following radiation therapy as evidenced by slit lamp exam and external photography. Pre and post radiation MRI imaging of the affected area were also used as a means to monitor disease progression.

Results: Four symptomatic patients with localized periocular AL amyloidosis received external beam radiation therapy ranging from 20–30 Gy fractioned over 10–20 fractions. Three of the four patients had prior surgical debulking with or without ptosis repair. Amyloid deposition did not progress in any patient at one year. Further follow-up of two patients revealed amyloid progression at two years post radiation.

Conclusions: External beam radiation therapy for localized periocular AL amyloidosis demonstrated efficacy at halting disease progression at one year; however, the long-term efficacy is unknown. Monitoring of periocular amyloid is best achieved with slit lamp exam and external photography as opposed to MRI.     

Fine–mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans,Melanesians and Polynesians

Differentiated thyroid carcinoma (DTC) incidence is characterized by wide ethnic and geographic variations, with high incidence rates observed in Oceanian populations. Genome-wide association studies (GWAS) identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in the population of the EPITHYR consortium that includes Europeans, Melanesians and Polynesians to identify likely causal variants for DTC risk. We conducted a colocalization analysis using eQTLs data to determine the SNPs with the highest probability of causality.At 2q35, we highlighted rs16857609 located in DIRC3. This SNP has a high probability of causality in the three populations, and a significant association in Europeans (OR = 1.4, p = 1.9 x 10^-10). It is also associated with expression of DIRC3 and of the nearby gene IGFBP5 in thyroid tumour cells. At 8p12, we identified rs7844425 which was significantly associated with DTC in Europeans (OR = 1.32, p = 7.6 x 10^-8) and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in our dataset (OR = 1.2, p = 0.001). These SNPs are linked to the expression of NRG1 in thyroid tissue.Hence, our study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.