GMP production of [F]FE-PE2I on a TRACERLab FX2 N synthesis module, a radiotracer for in vivo PET imaging of the dopamine transport.

Background: Parkinson's disease is a neurodegenerative disorder that is characterized by a degeneration of the dopaminergic system. Dopamine transporter (DAT) positron emission tomography (PET) imaging has emerged as a powerful and non-invasive method to quantify dopaminergic function in the living brain. The PET radioligand, [F]FE-PE2I, a cocaine chemical derivative, has shown promising properties for in vivo PET imaging of DAT, including high affinity and selectivity for DAT, excellent brain permeability, and favorable metabolism.

Optimized, automated and cGMP-compliant synthesis of the HER2 targeting [Ga]Ga-ABY-025 tracer.

Background: The Affibody molecule, ABY-025, has demonstrated utility to detect human epidermal growth factor receptor 2 (HER2) in vivo, either radiolabelled with indium-111 (In) or gallium-68 (Ga). Using the latter, Ga, is preferred due to its use in positron emission tomography with superior resolution and quantifying capabilities in the clinical setting compared to In. For an ongoing phase II study (NCT05619016) evaluating ABY-025 for detecting HER2-low lesions and selection of patients for HER2-targeted treatment, the aim was to optimize an automated and cGMP-compliant radiosynthesis of [Ga]Ga-ABY-025.

One-Pot Synthesis of C-Labelled Primary Benzamides via Intermediate [ C]Aroyl Dimethylaminopyridinium Salts.

Electrophilic C-labelled aroyl dimethylaminopyridinium salts, obtained by carbonylative cross-coupling of aryl halides with [ C]carbon monoxide, were prepared for the first time and shown to be valuable intermediates in the synthesis of primary [ C]benzamides. The methodology furnished a set of benzamide model compounds, including the two poly (ADP-ribose) polymerase (PARP) inhibitors niraparib and veliparib, in moderate to excellent radiochemical yields. In addition to providing a convenient and practical route to primary [ C]benzamides, the current method paves the way for future application of [ C]aroyl dimethylaminopyridinium halide salts in positron emission tomography (PET) tracer synthesis.

Development of a fully automated low-pressure [ C]CO carbonylation apparatus.

[ C]carbon monoxide ([ C]CO) is a versatile synthon for radiolabeling of drug-like molecules for imaging studies with positron emission tomography (PET). We here report the development of a novel, user-friendly, fully automated, and good manufacturing practice (GMP) compliant low-pressure synthesis module for C-carbonylation reactions using [ C]CO. In this synthesis module, [ C]CO was reliably prepared from cyclotron-produced [ C]carbon dioxide ([ C]CO ) by reduction over heated molybdenum and delivered to the reaction vessel within 7 min after end of bombardment, with an overall radiochemical yield (RCY) of 71%.

"In-loop" carbonylation-A simplified method for carbon-11 labelling of drugs and radioligands.

Transition-metal mediated carbonylation with C-labelled carbon monoxide ([ C]CO) is a versatile method for introducing C (t = 20.3 min) into drugs and radioligands for subsequent use in positron emission tomography (PET). The aim of the current study was to perform the C-carbonylation reaction on the interior surface of a stainless-steel loop used for high performance liquid chromatography (HPLC).