[68 Ga]Ga-PentixaFor: Development of a fully automated in hospital production on the Trasis miniAllinOne synthesizer.

[68 Ga]Ga-PentixaFor is a frequently used radiotracer to image the CXCR4/CXCL12 axis in various malignancies, infections, and cardiovascular diseases. To answer increasing clinical needs, an automatized synthesis process ensuring efficient and reproducible production and improving operator's radioprotection is needed. [68 Ga]Ga-PentixaFor synthesis has been described on other synthesizers but not on the miniAiO. In this work, we defined automated synthesis process and an analytical method for the quality control of [68 Ga]Ga-PentixaFor. Validation batches were performed under aseptic conditions in a class A hotcell. All the quality controls required by the European Pharmacopea (Eur. Ph) were performed. The analytical methods were validated according to the International Conference Harmonization (ICH) recommendations. Validation batches were performed with a radiochemical yield of 94.8 ± 2.6%. All the quality controls were in conformity with the Eur. Ph, and the validation of the analytical method complied with the ICH. The environmental monitoring performed during the synthesis process showed that the aseptic conditions were ensured. [68 Ga]Ga-PentixaFor was successfully synthesized with the miniAiO by a fully automated process. This robust production mode and the quality control have been validated in this study allowing to increase the access of patients to this new promising radiopharmaceutical.

Correction: Pacelli et al. Fully Automated, High-Dose Radiosynthesis of [18F]PARPi. Pharmaceuticals 2022, 15, 865.

Corentin Warnier, Thibault Gendron, Muhammad Otabashi, Charles Vriamont and Alex Jackson were not included as authors in the original publication [...].

multi-patient dose synthesis of [18F]Flumazenil via a copper-mediated 18F-fluorination.

BACKGROUND: Flumazenil (FMZ) is a functionally silent imidazobenzodiazepine which binds to the benzodiazepine binding site of approximately 75% of the brain γ-aminobutyric acid-A receptors (GABAARs). Positron Emission Tomography (PET) imaging of the GABAARs with [11C]FMZ has been used to evidence alterations in neuronal density, to assess target engagement of novel pharmacological agents, and to study disorders such as epilepsy and Huntington's disease. Despite the potential of FMZ PET imaging the short half-life (t1/2) of carbon-11 (20 min) has limited the more widespread clinical use of [11C]FMZ. The fluorine-18 (18F) isotopologue with a longer t1/2 (110 min) is ideally suited to address this drawback. However, the majority of current radiochemical methods for the synthesis of [18F]FMZ are non-trivial and low yielding. We report a robust, automated protocol that is good manufacturing practice (GMP) compatible, and yields multi-patient doses of [18F]FMZ. RESULTS: The fully automated synthesis was developed on the Trasis AllinOne (AIO) platform using a single-use cassette. [18F]FMZ was synthesized in a one-step procedure from [18F]fluoride, via a copper-mediated 18F-fluorination of a boronate ester precursor. Purification was performed by semi-preparative radio-HPLC and the collected fraction formulated directly into the final product vial. The overall process from start of synthesis to delivery of product is approximately 55 min. Starting with an initial activity of 23.6 ± 5.8 GBq (n = 3) activity yields of [18F]FMZ were 8.0 ± 1 GBq (n = 3). The synthesis was successfully reproduced at two independent sites, where the product passed quality control release criteria in line with the European Pharmacopoeia standards and ICH Q3D(R1) guidelines to be suitable for human use. CONCLUSION: Reported is a fully automated cassette-based synthesis of [18F]FMZ that is Good Manufacturing Practice (GMP) compatible and produces multi-patient doses of [18F]FMZ.

Automated synthesis of 68 Ga/177 Lu-PSMA on the Trasis miniAllinOne.

Prostate-specific membrane antigen (PSMA)-based radioligands for positron emission tomography (PET)/computed tomography (CT) studies represent the gold standard for detection of recurrent prostate cancer (PCa). [68 Ga]PSMA-HBED-CC is a PET radiotracer suitable for detection of PCa, and its clinical use has become widespread over the last few years. In this contribution, we detail our GMP-compliant production of [68 Ga]PSMA-HBED-CC using the Trasis miniAllinOne radiosynthesizer and report synthetic and clinical data for the first 100 productions of 2019. Additionally, we detail our efforts towards a GMP-compliant production of the radiotherapeutic [177 Lu]PSMA-I&T using the same synthesis module. PSMA-based radioligand therapy (RLT) offers a possible future treatment in cases of metastatic castration-resistant PCa, and GMP-compliant routine production methods are therefore called for. This report highlights how PSMA-based agents for theranostic purposes can be conveniently produced at a single radiochemistry Good Manufacturing Practice (GMP) site, thereby facilitating optimized detection and treatment of PCa.

A covalently anchored homogeneous gold complex on carbon nanotubes: a reusable catalyst.

The gold complex [Tf2NAuPPh3CH2NH2] was synthesized and covalently anchored on modified carbon nanotubes in order to obtain a supported gold homogeneous catalyst. Simple 1,6 enynes were chosen as benchmark substrates to assess its behaviour in cyclization catalysis as well as study its recycling.

Catalysis with Gold Complexes Immobilised on Carbon Nanotubes by π-π Stacking Interactions: Heterogeneous Catalysis versus the Boomerang Effect.

A new pyrene-tagged gold(I) complex has been synthesised and tested as a homogeneous catalyst. First, a simple 1,6-enyne was chosen as a model substrate for cyclisation by using different solvents to optimise the reaction conditions. The non-covalent immobilisation of our pyrene-tagged gold complex onto multi-walled carbon nanotubes through π-π stacking interactions was then explored to obtain a supported homogeneous catalyst. The heterogenised catalyst and its homogeneous counterpart exhibited similar activity in a range of enyne cyclisation reactions. Bearing in mind that π-π interactions are affected by temperature and solvent polarity, the reuse and robustness of the supported homogeneous catalyst was tested to explore the scope and limitations of the recyclability of this catalyst. Under the optimised conditions, recyclability was observed by using the concept of the boomerang effect.

Radical addition of xanthates on carbon nanotubes as an efficient covalent functionalization method.

Radical-initiated support: Xanthates were used as chemical reagents for the sidewall covalent functionalization of carbon nanotubes (see figure). The best grafting yields were obtained with stoichiometric ratios of xanthate and the radical initiator lauroyl peroxide. One grafted function was used as a tether for bimetallic cluster compounds, which were converted into very small (1-2 nm) supported nanoparticles upon heating.