Thera4Care researchers set out a reproducible route towards clinical-grade scandium-44
New study in EJNMMI Radiopharmacy and Chemistry addresses long-standing production challenges for a promising PET imaging radionuclide
Researchers working within the Thera4Care consortium have published an optimised method for producing, purifying, and radiolabelling scandium-44, an emerging radionuclide for positron emission tomography (PET) imaging. The paper, Unlocking the potential of scandium-44: reproducible production and radiolabelling methods towards clinical use in nuclear medicine, was published as an Article in Press on 30 September 2026. The authors are Chiara Favaretto, Anzhelika N. Moiseeva, Pascal V. Grundler, Marie G. Théry, Darja Beyer, Vitor R. Barrote, Hui Zhang, Alexander Sommerhalder, Roger Schibli, Lars F. Gerchow, Cristina Müller, and Nicholas P. van der Meulen, from the Paul Scherrer Institute (PSI), ETH Zurich, and IRCCS Sacro Cuore Don Calabria.
Why scandium-44?
Radiotheranostics pairs a diagnostic radiopharmaceutical with a therapeutic one so that clinicians can image where a treatment will accumulate before giving it. The prediction is most reliable when both radionuclides share similar chemistry. Today, however, imaging and therapy often rely on radionuclides with different chemical properties.
Scandium-44 offers several advantages for imaging:
Its chemistry resembles that of the therapeutic radionuclides lutetium-177 and terbium-161.
Its image resolution is comparable to radionuclides in routine clinical PET use.
Its half-life of around four hours allows the product to be transported and patients to be imaged later after injection.
The main obstacle has been production. Previous methods often gave inconsistent pH, purity, and activity concentration, which made reliable radiolabelling challenging.
Key findings
The team produced scandium-44 by irradiating enriched calcium-44 targets with protons at two facilities: a research cyclotron at PSI and a medical cyclotron at ETH Zurich. After testing several separation resins, they developed a two-step purification process. The study found that:
both sites achieved the same average production yield, which supports the reproducibility of the process
a single run yielded up to 4.4 GBq of purified scandium-44
radionuclidic purity exceeded 99%, and most metal contaminants were below European Pharmacopoeia limits
the final product had a consistent pH of 4, so it could be used for radiolabelling without further adjustment
scandium-44 was labelled to the peptide DOTATOC and to a second ligand with high radiochemical purity in repeated batches
In a proof-of-concept run, the team also used an automated synthesis module to produce a scandium-44-labelled DOTATOC formulation with more than 99% radiochemical purity. The quantity was sufficient for at least two patient doses. Automation matters for clinical use because it reduces operator radiation exposure and supports consistent manufacturing.
Relevance to theranostics and to Thera4Care
Reliable access to high-quality radionuclides is a prerequisite for bringing new radiotheranostic approaches to patients. This study contributes to Thera4Care's Work Package 4 (Supply & Production), which aims to establish standardised, reproducible production and supply of theranostic radionuclides across Europe. In particular, it supports the production and labelling of the scandium-44/terbium-161 pair with FAP-targeting agents. The results also lay groundwork for a possible early-phase diagnostic PET study with scandium-44 in WP5.
The authors note that further work is needed. Next steps include refining specifications for clinical use, recycling the costly enriched calcium-44 target material, and integrating the process into Good Manufacturing Practice (GMP) workflows.
