Clinical Trial: Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3)

Update 14th December 2025 – Results from the Phase 0 proof of concept trial.

Conclusion

[¹⁶¹Tb]Tb-DOTA-LM3 shows a 7.6-fold-higher tumor absorbed dose than that found when using [¹⁷⁷Lu]Lu-DOTATOC. The tumor–to–bone marrow absorbed dose ratio was in the same range for both radiopharmaceuticals. The promising dosimetry and safety results from this phase 0 study will lay the foundation for further clinical development of [¹⁶¹Tb]Tb-DOTA-LM3. Dose-escalation trials and peptide dose optimizing studies are warranted to establish the maximum tolerated activity per cycle and assess long-term efficacy. The integration of ¹⁶¹Tb into PRRT regimens has the potential to redefine the therapeutic landscape for NETs, particularly for patients with suboptimal responses to current treatments or possible treatment of micrometastases.

Read the full report by clicking here Notes from Ronny. Some people are calling this ‘beta plus’ indicating it’s more advanced than regular beta emitter PRRT out there. But other sources suggest this is a new form of PRRT to compete with beta-emitter (e.g. Lu177 Lutathera) and alpha-emitter versions currently in clinical trials (225AC and 212Pb versions). What is the plus? What makes it beta plus is auger electrons. These are tiny particles of energy released when certain radioactive medicines break down inside a cell. They are much weaker and shorter‑ranged than the “beta particles” used in standard PRRT. i.e. instead of travelling millimetres, they only move a few nanometres (that’s smaller than the width of DNA). Why that matters Because they don’t travel far, Auger electrons only cause damage right where they are released. If the radioactive medicine gets close to the cell’s DNA, Auger electrons can cause very precise damage, making it harder for the cancer cell to repair itself. Unlike beta particles, they don’t “spill over” into nearby healthy tissue — they’re more like a scalpel than a shotgun. i.e. it’s more targeted than current PRRT treatment. Update 14th March 2024 – First-in-human administration of terbium-161-labelled somatostatin receptor subtype 2 antagonist ([¹⁶¹Tb]Tb-DOTA-LM3) in a patient with a metastatic neuroendocrine tumour of the ileum Here, the Basel sponsor reports on the first patient (78-year-old man) with a metastatic, hormone-active (carcinoid syndrome) ileal neuroendocrine tumour (G1, Ki-67, < 3%), who received a test infusion of 1 GBq [¹⁶¹Tb]Tb-DOTA-LM3 in an ongoing prospective Phase 0 study. So far, the patient received long-acting octreotide, which was stopped 2 months

First-in-human administration of terbium-161-labelled somatostatin receptor subtype 2 antagonist ([¹⁶¹Tb]Tb-DOTA-LM3) in a patient with a metastatic neuroendocrine tumour of the ileum. Julia Fricke, Frida Westerbergh, Lisa McDougall, Chiara Favaretto, Emanuel Christ, Guillaume P. Nicolas, Susanne Geistlich, Francesca Borgna, Melpomeni Fani, Peter Bernhardt, Nicholas P. van der Meulen, Cristina Müller, Roger Schibli & Damian Wild

Open access
Published: 07 March 2024

What is Terbium-161 (161Tb-DOTA-LM3) (Beta plus).

Terbium-161 is a radioactive substance. DOTA-LM3 is a novel somatostatin antagonist targeted using somatostatin receptor number 2 (SSTR2). Combined they form a radioligand for use in Peptide Receptor Radionuclide Therapy (PRRT). It’s a beta emitter but labelled ‘plus’ on the basis it offers more than the currently approved Luthatera product (lutetium 177 or 177Lu Dotaxxx series). There is evidence that terbium-161 (161Tb) is more powerful than 177Lu, not only in combination with SST2 agonists but particularly with SST2 antagonists. Agonist vs Antagonist in the context of PRRT The currently approved Lutathera product (lutetium 177 or 177Lu Dotaxxx series) are SST2 agonists. SST2 antagonists are more efficient because they can access more binding sites on the cell surface, resulting in higher tumour uptake and improved sensitivity.

Trial Summary

A new clinical trial being conducted at a single centre in Switzerland aims to explore a therapy using a novel somatostatin receptor subtype 2 antagonist labelled with Terbium-161 (161Tb-DOTA-LM3). The study is sponsored by University Hospital, Basel, in collaboration with the Swiss National Science Foundation and the Paul Sherrer Institute and builds upon research funded by NET Research Foundation (NETRF). The goal of the proof-of-concept study is to measure the therapeutic index of 161Tb-DOTA-LM3 in comparison to the current standard treatment with 177Lu-DOTATOC in gastroenteropancreatic neuroendocrine tumours (GEP-NET). Damian Wild, MD, PhD, leads the current proof-of-concept trial at University Hospital, Basel. The study will enrol up to 16 patients who have metastasized and non-secreting GEP-NETs (grade 1 and 2). Patients will be randomized into two treatment groups. In the first phase of the study, one test injection with 161Tb-DOTA-LM3 and 177Lu-DOTATOC will be administered in both randomized groups in a different order, followed by approximately 3 cycles of PRRT in both groups. In the second phase, two test injections with 161Tb-DOTA-LM3 with different peptide amounts will be administered in both treatment groups in a different order, followed by approximately two cycles of PRRT with 161Tb-DOTA-LM3. Additional information on the study can be found at the link below. Interested participants should talk to their treatment team about eligibility and determine if the study is aligned with their treatment goals. I also draw your attention to the inclusion and exclusion criteria in the clinical trials document linked below.

Why is this trial important?

Although PRRT is one of the most efficient treatments for the management of NENs, it does only stabilize but not cure the disease. There is a need to improve PRRT with more effective radiopharmaceuticals. There is evidence that terbium-161 (161Tb) is more powerful that 177Lu not only in combination with SST2 agonists but particularly with SST2 antagonists. The efficacy of PRRT can be enhanced by using a potent SST2 antagonist (DOTA-LM3) labelled with 161Tb. 161Tb-DOTA-LM3 has the following advantages compared to 177Lu-DOTATOC and 177Lu-DOTATATE: 1) SST2 antagonists bind to many more SST2-binding sites and accumulate mainly on the cellular membrane. 2) The Auger electrons of 161Tb deposit their high energy over a short distance (1-1000 nm) resulting in a high relative biological effectiveness mainly to the cell membrane which seems to be more radiosensitive than the cytoplasm. 161Tb-DOTA-LM3 does, therefore, not only deliver dose by β- radiation (beta radiation), but also through the emission of conversion and Auger electrons which leads to a 3 to 4-fold increased dose to single cancer cells compared to 177Lu-DOTA-LM3 (thus the “plus” annotation as this effect is something seen in alpha emitter therapy).

Terbium-161: new radionuclide therapy hits the clinic

This is a useful summary which gives you an idea of the potential of Terbium-161.

“It’s all about how terbium emits its electrons, he explains. Both terbium-161 and lutetium-177 are beta-emitters. What’s more, they both possess a similar half-life of just under seven days. But terbium-161 emits in addition abundant low-energy so-called conversion and Auger electrons. These deliver a punch of radiation over a short distance – within the cancer cell.” Read more – click here.

The radiopharmaceutical consists of a radioactive molecule – in this case terbium-161 linked to a ligand. This ligand recognises proteins on the tumour cell, allowing highly targeted cancer treatment. Now, it is being tested in patients for prostate cancer and neuroendocrine tumours. (Image: Ella Maru Studios)

……and it is even being tested as an alpha-emitter version – click here Read more here

Resources

1. ClinicalTrials.gov Identifier: NCT05359146.
2. Pre-clinical and first in human study – click here.
3. Combination of terbium-161 with somatostatin receptor antagonists—a potential paradigm shift for the treatment of neuroendocrine neoplasms | SpringerLink
4. Terbium Triumph | Labs & User Services | Paul Scherrer Institute (PSI)
5. Terbium-161: new radionuclide therapy hits the clinic
6. Peptide Receptor Radionuclide Therapy (PRRT) Using Actinium-225- and Ac-225/Lutetium-177-Labeled (TANDEM) Somatostatin Receptor Antagonist DOTA-LM3 in Patients with Neuroendocrine Neoplasm: A Retrospective Study Concerning Safety and Survival Results of an earlier study can be found here, and the conclusion has led to this formal clinical trial above. Click here or on the picture to read more.

General Clinical Trials Disclaimer

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact. If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional. Some content may be generated by AI which can sometimes be misinterpreted. Please check any references attached. Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

Finally

Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product. Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document. Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET