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

Source: https://nuclide.cc/ideas/idea-tb161-instead-of-lu177/  
Nuclide record `idea-tb161-instead-of-lu177` (Idea). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Terbium-161 is a close chemical cousin of lutetium-177 that, as well as giving off the same kind of radiation, also releases a shower of extremely short-range electrons. In theory that extra radiation could finish off single cancer cells and tiny clusters that a lutetium-177 treatment might miss, using the same targeting molecules already in use.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-22
- Tags: prostate; isotope alternative; auger electrons
- Hypothesis: Substituting terbium-161 for lutetium-177 in the same PSMA or somatostatin-receptor ligand will produce a higher objective response rate at an equivalent kidney and salivary-gland radiation dose, because terbium-161's additional Auger and conversion electrons deposit extra lethal energy in micrometastases that lutetium-177's longer-range beta particles largely miss.
- Rationale: Preclinical dosimetry work (Müller et al., Grünberg et al., Champion et al.) consistently found terbium-161 delivers several-fold higher absorbed dose than lutetium-177 to single cells and small tumour clusters, and dual-isotope SPECT imaging confirmed the two radiolanthanides are pharmacokinetically interchangeable when attached to the same peptide. The first-in-human VIOLET trial (30 patients) showed 161Tb-PSMA-I&T is safe with organ doses comparable to 177Lu-PSMA-617, but was single-arm and not powered to detect an efficacy difference. No completed trial has yet reported a head-to-head efficacy comparison.
- Proposed test: A randomised phase 2 trial in metastatic castration-resistant prostate cancer comparing 161Tb-PSMA-I&T against 177Lu-PSMA-617 at kidney-dose-matched activities, powered on PSA50 response rate or PSMA-PET-defined progression-free survival, roughly 150-200 patients; the ongoing REALITY intra-individual dosimetry comparison (NCT04833517) is a smaller precursor step.
- Maturity: early-clinical
- Actor: research

## Sources

- Peter Mac / UCSF-UCLA PSMA Conference 2025: Michael Hofman on terbium-161 (VIOLET): https://www.urotoday.com/video-lectures/2025-ucsf-ucla-psma-conference/video/4752-beyond-lutetium-psma-exploring-terbium-161-for-treatment-resistant-prostate-cancer-presentation-michael-hofman.html
- Terbium-161 in nuclear medicine: preclinical and clinical status (PubMed, 2025): https://pubmed.ncbi.nlm.nih.gov/39978166/
- Opportunities and potential challenges of using terbium-161 for targeted radionuclide therapy in clinics (EJNMMI, 2023): https://link.springer.com/article/10.1007/s00259-023-06316-y
- From lutetium to terbium: a new era in PSMA-targeted radioligand therapy (PMC, 2025): https://pmc.ncbi.nlm.nih.gov/articles/PMC12629902/

## Connected records

- technologies: [Lutetium-177 radioligand therapy](https://nuclide.cc/technologies/lu177-radioligand-therapy/), [Peptide receptor radionuclide therapy (PRRT)](https://nuclide.cc/technologies/prrt/), [PSMA PET](https://nuclide.cc/technologies/psma-pet/), [Radioligand dosimetry](https://nuclide.cc/technologies/radioligand-dosimetry/)
- isotopes: [Lutetium-177](https://nuclide.cc/isotopes/lu-177/), [Terbium-161](https://nuclide.cc/isotopes/tb-161/)

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