New paper - Thera4Care researchers show terbium-161 could be a viable alternative to lutetium-177 for FAP-targeted cancer therapy

Preclinical study published in EJNMMI Research supports work on next-generation radioligand therapy for sarcoma

Researchers at the Paul Scherrer Institute (PSI) and ETH Zurich, working within the Thera4Care consortium, have published a new preclinical study comparing two candidate radionuclides for targeted cancer therapy: lutetium-177, already used in the clinic, and terbium-161, an emerging alternative. The paper, Preclinical characterisation of FAP-targeting radioconjugates: assessing biophysical and pharmacokinetic equivalence of lutetium-177 and terbium-161, was published in EJNMMI Research on 29 July 2026 and is authored by Ana Katrina Mapanao, Ecem Selin Adakli, Christian Vaccarin, Fan Sozzi-Guo, Anzhelika N. Moiseeva, Roger Schibli, Nicholas P. van der Meulen, Cristina Müller, and the Thera4Care Consortium.

Why this matters for theranostics

The study focuses on the fibroblast activation protein (FAP), a target expressed on the cancer-associated fibroblasts that make up much of the tumour microenvironment in many solid cancers, and, notably, directly on tumour cells in sarcoma. This dual role makes FAP an attractive target for radiotheranostics: pairing diagnostic imaging with matched radionuclide therapy so that treatment can be tailored to each patient.

Terbium-161 is of particular interest because, alongside beta-particle emission similar to lutetium-177, it also emits short-range Auger and conversion electrons, which may enhance its effect against small tumour deposits and micrometastases, while its co-emitted gamma radiation still allows SPECT imaging.

Key findings

Four FAP-inhibitor conjugates (FAPI-46, OncoFAP, FAP-2286 and 3BP-3940) were labelled with each radionuclide and evaluated in fibrosarcoma cells and in a mouse xenograft model. The researchers found that, regardless of which radionuclide was used, the radioconjugates:

• Remained highly stable (≥96% intact) in solution over 24 hours

• Showed closely matched binding affinity, cell uptake and lipophilicity

• Displayed comparable blood plasma protein binding and stability

• Produced corresponding distribution profiles in mice on dual-isotope SPECT/CT imaging and biodistribution studies, with rapid blood clearance and tumour uptake of up to 20% of the injected activity per gram at one hour post-injection

Tumour retention declined over time for most conjugates, indicating that repeated administration would likely be needed to achieve a therapeutic effect, an important consideration for future dosing strategies.

Contribution to Thera4Care's goals

These results provide preclinical evidence that terbium-161 can be considered pharmacokinetically equivalent to lutetium-177 across a range of FAP-targeting agents. This directly supports Thera4Care's investigation of terbium-161-based radioligand therapy in sarcoma, ovarian and pancreatic cancers, one of the clinical applications the consortium is working to bring closer to patients. By confirming that existing FAP inhibitors behave consistently across both radionuclides, the study strengthens the scientific basis for selecting and advancing candidate agents towards Thera4Care's planned early-phase clinical studies, and contributes to the consortium's broader ambition of expanding Europe's radiotheranostics capacity and treatment options for cancers with limited existing therapies.