Terbium-161 instead of lutetium-177 in the same ligands

Terbium-161 decays with a half-life of about 6.95 days and emits beta particles similar in energy to lutetium-177's, plus roughly ten times more conversion and Auger electrons per decay. These electrons travel only nanometres to micrometres, so preclinical dosimetry modelling (Champion et al.; Müller et al.) predicts 2-3-fold higher absorbed dose to single cells and micrometastases than lutetium-177 at the same injected activity, while producing only modestly higher organ doses to kidney and salivary gland. Because terbium-161 is chemically a lanthanide like lutetium-177, the same DOTA-based chelators and labelling protocols can be reused for PSMA and somatostatin-receptor ligands.

Clinical translation is under way but not yet comparative. The first-in-human VIOLET trial at Peter MacCallum Cancer Centre (NCT05521412, 30 patients with metastatic castration-resistant prostate cancer) established that 161Tb-PSMA-I&T is feasible and safe up to 7.4 GBq, with organ doses similar to historical 177Lu-PSMA-617 data, and the study has since opened a 9.5 GBq expansion cohort. A German programme (REALITY, NCT04833517) is running an intra-individual head-to-head dosimetry comparison of 161Tb-PSMA-617 against 177Lu-PSMA-617 in the same patients. Neither trial has yet reported a comparative efficacy result, and global terbium-161 supply remains a research-scale bottleneck: the reactor-based no-carrier-added production route needed to avoid stable terbium contamination is far less mature than lutetium-177 supply chains.

The open question is whether the extra subcellular dose actually translates into better tumour control at a clinically tolerable normal-organ dose, rather than just a favourable dosimetry ratio in phantoms and mice.