Improved purification of cyclotron [Ga]GaCl for the production of Ga radiopharmaceuticals.

Introduction: Increased demand for NetSpot and Illuccix as requirement to receive the respective Lutathera and Pluvicto radiotherapies, and monitor subsequent response to treatment, have reinforced the need to develop alternative ways of producing gallium-68 (Ga). Building on our efforts to produce Ga in a liquid target on a GE PETtrace, the goal of this work is to modify the current GE Gallium Chloride cassette using the FASTLab 2 synthesis module to produce [Ga]GaCl equivalent to a 1.85 GBq generator and demonstrate compatibility with FDA-approved kits for production of Ga-labeled radiopharmaceuticals.

Automated production of [C]butyrate for keto body PET imaging.

The report describes an updated, fully automated method for the production of [C]butyrate, validated for use in clinical studies. A commercially available GE Tracerlab FX synthesis module was reconfigured to allow for air-free introduction of n-propyl magnesium chloride and to incorporate Sep-Pak cartridges to simplify and shorten the purification process, as compared to purifying the product using traditional HPLC. The method takes 20 min from end-of-bombardment and reliably produces injectable doses of [C]butyrate (8029 ± 1628 MBq (217 ± 44 mCi), 14 % radiochemical yield based on [C]CO non-decay corrected) in high radiochemical purity (>97 %), n = 3.

Potential Applications of Artificial Intelligence and Machine Learning in Radiochemistry and Radiochemical Engineering.

Artificial intelligence and machine learning are poised to disrupt PET imaging from bench to clinic. In this perspective, the authors offer insights into how the technology could be applied to improve the radiosynthesis of new radiopharmaceuticals for PET imaging, including identification of an optimal labeling approach as well as strategies for radiolabeling reaction optimization.

Synthesis and evaluation of NLRP3-inhibitory sulfonylurea [C]MCC950 in healthy animals.

The diaryl sulfonylurea MCC950/CRID3 is a potent NLRP3 inhibitor (IC = 8 nM) and, in animal models, MCC950 protects against numerous NLRP3-related neurodegenerative disorders. To evaluate the brain uptake and investigate target engagement of MCC950, we synthesised [C-urea]MCC950 via carrier added [C]CO fixation chemistry (activity yield = 237 MBq; radiochemical purity >99%; molar activity = 7 GBq/µmol; radiochemical yield (decay-corrected from [C]CO) = 1.1%; synthesis time from end-of-bombardment = 31 min; radiochemically stable for >1 h).

Synthesis and evaluation of [(11)C]PyrATP-1, a novel radiotracer for PET imaging of glycogen synthase kinase-3β (GSK-3β).

Introduction: The dysfunction of glycogen synthase kinase-3β (GSK-3β) has been implicated in a number of diseases, including Alzheimer's disease. The ability to non-invasively quantify GSK-3β activity in vivo is therefore of critical importance, and this work is focused upon development of inhibitors of GSK-3β radiolabeled with carbon-11 to examine quantification of the enzyme using positron emission tomography (PET) imaging.

Methods: (11)C PyrATP-1 was prepared from the corresponding desmethyl-piperazine precursor in an automated synthesis module.

Ethanolic carbon-11 chemistry: the introduction of green radiochemistry.

The principles of green chemistry have been applied to a radiochemistry setting. Eleven carbon-11 labeled radiopharmaceuticals have been prepared using ethanol as the only organic solvent throughout the entire manufacturing process. The removal of all other organic solvents from the process simplifies production and quality control (QC) testing, moving our PET Center towards the first example of a green radiochemistry laboratory.