Production of [F]DPA-714, [F]fallypride and [F]LBT-999 using iMiDEV, a fully automated microfluidic platform: towards clinical radiopharmaceutical production.

Background: Positron emission tomography is widely used to study biological processes without disrupting normal physiological functions. Traditional radiotracer synthesis and industrial market is focused on producing large batches of F-labelled tracers, especially [F]FDG. Accessibility to smaller quantity of diverse radiopharmaceuticals is a key to enable a more personalised approach in nuclear medicine.

Impaired Gait, Postural Instability, and Rigidity in Relation to CB1 Receptor Availability in Parkinson's Disease.

Background: In Parkinson's disease (PD), postural instability and gait disorder (PIGD) symptoms are associated with a worse prognosis for an unknown reason.

Objective: The objective was to explore the relationship between cannabinoid receptor type 1 (CB1R) availability and motor symptoms in PD with [F]FMPEP-d positron emission tomography (PET).

Methods: Fifteen individuals with PD underwent [F]FMPEP-d PET to measure cerebral CB1R availability.

Non-invasive quantification of stem cell-derived islet graft size and composition.

Aims/hypothesis: Stem cell-derived islets (SC-islets) are being used as cell replacement therapy for insulin-dependent diabetes. Non-invasive long-term monitoring methods for SC-islet grafts, which are needed to detect misguided differentiation in vivo and to optimise their therapeutic effectiveness, are lacking. Positron emission tomography (PET) has been used to monitor transplanted primary islets.

[F]fluoride Activation and F-Labelling in Hydrous Conditions-Towards a Microfluidic Synthesis of PET Radiopharmaceuticals.

F-labelled radiopharmaceuticals are indispensable in positron emission tomography. The critical step in the preparation of F-labelled tracers is the anhydrous F-18 nucleophilic substitution reaction, which involves [F]F anions generated in aqueous media by the cyclotron. For this, azeotropic drying by distillation is widely used in standard synthesisers, but microfluidic systems are often not compatible with such a process.

Cannabinoid Receptor Type 1 in Parkinson's Disease: A Positron Emission Tomography Study with [ F]FMPEP-d.

Background: The endocannabinoid system is a widespread neuromodulatory system affecting several biological functions and processes. High densities of type 1 cannabinoid (CB1) receptors and endocannabinoids are found in basal ganglia, which makes them an interesting target group for drug development in basal ganglia disorders such as Parkinson's disease (PD).

Objective: The aim of this study was to investigate CB1 receptors in PD with [ F]FMPEP-d positron emission tomography (PET) and the effect of dopaminergic medication on the [ F]FMPEP-d binding.

Safety, Biodistribution, and Radiation Dosimetry of F-rhPSMA-7.3 in Healthy Adult Volunteers.

This first-in-humans study investigated the safety, biodistribution, and radiation dosimetry of a novel F-labeled radiohybrid prostate-specific membrane antigen (rhPSMA) PET imaging agent, F-rhPSMA-7.3. Six healthy volunteers (3 men, 3 women) underwent multiple whole-body PET acquisitions at scheduled time points up to 248 min after the administration of F-rhPSMA-7.

Ruthenium-Mediated F-Fluorination and Preclinical Evaluation of a New CB Receptor Imaging Agent [F]FPATPP.

Cannabinoid receptor 1 (CB1R) controls various physiological and pathological conditions, including memory, motivation, and inflammation, and is thus an interesting target for positron emission tomography (PET). Herein, we report a ruthenium-mediated radiolabeling synthesis and preclinical evaluation of a new CB1R specific radiotracer, [F]FPATPP. [F]FPATPP was produced with 16.

Automated GMP production and long-term experience in radiosynthesis of CB tracer [ F]FMPEP-d.

Here, we describe the development of an in-house-built device for the fully automated multistep synthesis of the cannabinoid CB receptor imaging tracer (3R,5R)-5-(3-([ F]fluoromethoxy-d )phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([ F]FMPEP-d ), following good manufacturing practices. The device is interfaced to a HPLC and a sterile filtration unit in a clean room hot cell. The synthesis involves the nucleophilic F-fluorination of an alkylating agent and its GC purification, the subsequent F-fluoroalkylation of a precursor molecule, the semipreparative HPLC purification of the F-fluoroalkylated product, and its formulation for injection.

Fast and efficient copper-mediated F-fluorination of arylstannanes, aryl boronic acids, and aryl boronic esters without azeotropic drying.

Background: Copper-mediated radiofluorination is a straightforward method to produce a variety of [F]fluoroarenes and [F]fluoroheteroarenes. To minimize the number of steps in the production of F-labelled radiopharmaceuticals, we have developed a short and efficient azeotropic drying-free F-labelling method using copper-mediated fluorination. Our goal was to improve the copper-mediated method to achieve wide substrate scope with good radiochemical yields with short synthesis time.

Radiosynthesis of the norepinephrine transporter tracer [ F]NS12137 via copper-mediated F-labelling.

[ F]NS12137 (exo-3-[(6-[ F]fluoro-2-pyridyl)oxy]8-azabicyclo[3.2.1]octane) is a highly selective norepinephrine transporter (NET) tracer.

Cannabinoid Type 1 Receptors Are Upregulated During Acute Activation of Brown Adipose Tissue.

Activating brown adipose tissue (BAT) could provide a potential approach for the treatment of obesity and metabolic disease in humans. Obesity is associated with upregulation of the endocannabinoid system, and blocking the cannabinoid type 1 receptor (CB1R) has been shown to cause weight loss and to decrease cardiometabolic risk factors. These effects may be mediated partly via increased BAT metabolism, since there is evidence that CB1R antagonism activates BAT in rodents.

2,6-Bis(1,4,7,10-tetraazacyclododecan-1-ylmethyl)pyridine and Its Benzene Analog as Nonmetallic Cleaving Agents of RNA Phosphodiester Linkages.

2,6-Bis(1,4,7,10-tetraazacyclododecan-1-ylmethyl)pyridine (11a) and 1,3-bis(1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene (11b) have been shown to accelerate at 50 mmol·L-1 concentration both the cleavage and mutual isomerization of uridylyl-3',5'-uridine and uridylyl-2',5'-uridine by up to two orders of magnitude. The catalytically active ionic forms are the tri- (in the case of 11b) tetra- and pentacations. The pyridine nitrogen is not critical for efficient catalysis, since the activity of 11b is even slightly higher than that of 11a.