The complete workflow must also be robust, reproducible, transferable and compatible with the operational realities of hospital radiopharmacy.

This was the challenge addressed by Trasis and the CHRU of Nancy through the development and validation of a standardised automated radiosynthesis process for [⁶⁸Ga]Ga-NODAGA-exendin-4, a PET imaging tracer used to support the localisation of insulinomas.

The results have now been published as an open-access article in EJNMMI Radiopharmacy and Chemistry.

Why insulinomas remain difficult to localise

Insulinomas are rare pancreatic neuroendocrine tumours that produce excessive amounts of insulin and can cause recurrent episodes of hypoglycaemia.

Because these tumours are often small and located within the pancreas, they can be difficult to detect using conventional anatomical imaging methods.

PET imaging targeting the glucagon-like peptide-1 receptor, which is strongly expressed in most insulinomas, offers a valuable complementary approach. Among the tracers developed for this purpose, [⁶⁸Ga]Ga-NODAGA-exendin-4 has demonstrated strong diagnostic potential.

However, its broader routine clinical use has remained limited by the lack of a harmonised and easily transferable production process.

From a promising tracer to a transferable production process

The process was initially developed and optimised by Trasis using the miniAllinOne synthesiser, together with adapted Trasis cassettes and reagent kits.

Rather than focusing solely on the radiolabelling reaction, the Trasis team reassessed the complete production workflow, from precursor handling and synthesis sequence to formulation, residual activity and quality control.

Several critical parameters were systematically evaluated, including:

precursor quantity;
radiolabelling temperature and duration;
sequence of the synthesis steps;
product formulation;
reduction of residual activity within the cassette and tubing;
stability of the radiolabelled product;
quality control conditions.

The final process uses 20 µg of precursor and a radiolabelling step performed at 95 °C for 12 minutes.

The addition of polysorbate 20 after radiolabelling helped reduce product adsorption within the cassette and tubing. Antioxidants were also incorporated into the formulation to limit degradation over time, with product stability maintained for up to four hours after production.

Reproducible performance across three gallium-68 generators

Across the validation studies, non-decay-corrected radiochemical yields ranged from 60% to 73%, while decay-corrected yields reached up to 93%.

The highest yields were obtained after incorporating antioxidants into the optimised formulation.

Radiochemical purity consistently exceeded 95%, and all validation batches met the predefined quality control specifications.

The process was successfully evaluated with gallium-68 generators from three different manufacturers, demonstrating consistent performance across the three platforms tested.

This flexibility is particularly relevant for hospital radiopharmacies, where generator configurations, equipment and production environments may vary from one centre to another.

For hospital teams, reproducibility is not only a technical performance indicator. It supports more predictable production, consistent product quality and greater confidence in routine operations.

Hospital transfer driving further process improvement

The collaboration between Trasis and the CHRU of Nancy was central to demonstrating the transferability of the process.

After its initial development and optimisation at Trasis, the radiosynthesis procedure was transferred to the CHRU of Nancy and evaluated using the hospital’s own miniAllinOne system, gallium-68 generator and quality control equipment.

This transfer was not simply a final validation step.

The hospital-based work helped identify a product stability challenge that was then further investigated and addressed through formulation improvements and the evaluation of antioxidants.

The project brought together Trasis specialists in radiochemistry, automation, consumable development and analytical methods with the practical expertise of a hospital radiopharmacy team.

This iterative collaboration helped ensure that the final process was not only technically efficient, but also better suited to real-world radiopharmacy conditions.

Supporting more consistent insulinoma PET production

By integrating synthesis optimisation, generator-compatible consumables, formulation improvements and adapted quality control methods, the study establishes a practical foundation for more reproducible preparation of [⁶⁸Ga]Ga-NODAGA-exendin-4 in hospital radiopharmacies.

It also illustrates how close collaboration between technology developers and clinical teams can help transform a promising radiopharmaceutical into a process that is more robust, transferable and compatible with routine practice.

Read the scientific publication

High-yield, standardised automated radiosynthesis process for routine clinical insulinoma PET with [⁶⁸Ga]Ga-NODAGA-exendin-4

Published in EJNMMI Radiopharmacy and Chemistry.

Standardised Automated [⁶⁸Ga]Ga-NODAGA-Exendin-4 Radiosynthesis on miniAllinOne for Insulinoma PET

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