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[68Ga]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. [68Ga]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 [68Ga]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. [68Ga]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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [68Ga]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 [68Ga]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 [177Lu]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. [ABSTRACT FROM AUTHOR]

We herein describe the straightforward synthesis of a stable pyridyl(4-methoxyphenyl)iodonium salt and its [18F] radiolabeling within a one-step, fully automated and cGMP compliant radiosynthesis of [18F]UCB-H ([18F]7), a PET tracer for the imaging of synaptic vesicle glycoprotein 2A (SV2A). Over the course of 1 year, 50 automated productions provided 34 ± 2% of injectable [18F]7 from up to 285 GBq (7.7 Ci) of [18F]fluoride in 50 min (uncorrected radiochemical yield, specific activity of 815 ± 185 GBq/μmol). The successful implementation of our synthetic strategy within routine, high-activity, and cGMP productions attests to its practicality and reliability for the production of large doses of [18F]7. In addition to enabling efficient and cost-effective clinical research on a range of neurological pathologies through the imaging of SV2A, this work further demonstrates the real value of iodonium salts for the cGMP 18F-PET tracer manufacturing industry, and their ability to fulfill practical and regulatory requirements in that field. [ABSTRACT FROM AUTHOR]

[ 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., (© 2023 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.)

Lung PET/CT is a promising imaging modality for regional lung function assessment. Our aim was to develop and validate a fast, simple, and fully automated GMP compliant [ 68 Ga]Ga-MAA labeling procedure, using a commercially available [ 99m Tc]Tc-MAA kit, a direct gallium-68 eluate and including a purification of the [ 68 Ga]Ga-MAA. Method: The synthesis parameters (pH, heating temperature) were manually determined. Automated 68 Ga-labeling of MAA was then developed on a miniAIO (Trasis®, Ans, Belgium) module. An innovative automated process was developed for the purification. The process was then optimized and adapted to automate both the [ 68 Ga]Ga-MAA synthesis and the isolation of gallium-68 eluate required for the pulmonary ventilation PET/CT. Results: The 15-min process demonstrated high reliability and reproducibility, with high synthesis yield (>95 %). Mean [ 68 Ga]Ga-MAA radiochemical purity was 99 % ± 0.6 %. The 68 Ga-labeled MAA particles size and morphology remained unchanged. Conclusion: A fast, user friendly, and fully automated process to produce GMP [ 68 Ga]Ga-MAA for clinical use was developed. This automated process combining the advantages of using a non-modified MAA commercial kit, a gallium-68 eluate without pre-purification and an efficient final purification of the [ 68 Ga]Ga-MAA may facilitate the implementation of lung PET/CT imaging in nuclear medicine departments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Blanc-Béguin, Masset, Robin, Tripier, Hennebicq, Guilloux, Vriamont, Warnier, Cogulet, Eu, Salaün and Le Roux.)

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., (© 2020 John Wiley & Sons, Ltd.)

The synaptic vesicle glycoprotein 2A (SV2A), a protein essential to the proper nervous system function, is found in presynaptic vesicles. Thus, SV2A targeting, using dedicated radiotracers combined with positron emission tomography (PET), allows the assessment of synaptic density in the living brain. The first-in-class fluorinated SV2A specific radioligand, [ 18 F]UCB-H, is now available at high activity through an efficient radiosynthesis compliant with current good manufacturing practices (cGMP). We report here a noninvasive method to quantify [ 18 F]UCB-H binding in rat brain with microPET. Validation study in rats confirmed the need of high enantiomeric purity to target SV2A in vivo. We demonstrated the reliability of a population-based input function to quantify SV2A in preclinical microPET setting. Finally, we investigated the in vivo metabolism of [ 18 F]UCB-H and confirmed the negligible amount of radiometabolites in the rat brain. Hence, the in vivo quantification of SV2A using [ 18 F]UCB-H microPET seems a promising tool for the assessment of the synaptic density in the rat brain, and opens the way for longitudinal follow-up in neurodegenerative disease rodent models.

We herein describe the straightforward synthesis of a stable pyridyl(4-methoxyphenyl)iodonium salt and its [ 18 F] radiolabeling within a one-step, fully automated and cGMP compliant radiosynthesis of [ 18 F]UCB-H ([ 18 F]7), a PET tracer for the imaging of synaptic vesicle glycoprotein 2A (SV2A). Over the course of 1 year, 50 automated productions provided 34 ± 2% of injectable [ 18 F]7 from up to 285 GBq (7.7 Ci) of [ 18 F]fluoride in 50 min (uncorrected radiochemical yield, specific activity of 815 ± 185 GBq/μmol). The successful implementation of our synthetic strategy within routine, high-activity, and cGMP productions attests to its practicality and reliability for the production of large doses of [ 18 F]7. In addition to enabling efficient and cost-effective clinical research on a range of neurological pathologies through the imaging of SV2A, this work further demonstrates the real value of iodonium salts for the cGMP 18 F-PET tracer manufacturing industry, and their ability to fulfill practical and regulatory requirements in that field.

One of the most essential aspects to the success of radiopharmaceuticals is an easy and reliable radiolabelling protocol to obtain pure and stable products. In this study, we optimized the bioconjugation and gallium-68 ((68) Ga) radiolabelling conditions for a single-stranded 40-mer DNA oligonucleotide, in order to obtain highly pure and stable radiolabelled oligonucleotides. Quantitative bioconjugation was obtained for a disulfide-functionalized oligonucleotide conjugated to the macrocylic bifunctional chelator MMA-NOTA (maleimido-mono-amide (1,4,7-triazanonane-1,4,7-triyl)triacetic acid). Next, this NOTA-oligonucleotide bioconjugate was radiolabelled at room temperature with purified and pre-concentrated (68) Ga with quantitative levels of radioactive incorporation and high radiochemical and chemical purity. In addition, high chelate stability was observed in physiological-like conditions (37 °C, PBS and serum), in the presence of a transchelator (EDTA) and transferrin. A specific activity of 51.1 MBq/nmol was reached using a 1470-fold molar excess bioconjugate over (68) Ga. This study presents a fast, straightforward and reliable protocol for the preparation of (68) Ga-radiolabelled DNA oligonucleotides under mild reaction conditions and without the use of organic solvents. The methodology herein developed will be applied to the preparation of oligonucleotidic sequences (aptamers) targeting the human epidermal growth factor receptor 2 (HER2) for cancer imaging., (Copyright © 2015 John Wiley & Sons, Ltd.)