Investigational · Terbium-161

How does Terbium-161 compare to Lutetium-177?

Terbium-161 is an investigational radionuclide that combines beta emission with short-range Auger and conversion electrons — a physics profile of significant research interest, but one whose clinical value has not been established by randomised data. This article describes the physics, the early human studies, and what should and should not be claimed about Tb-161 today.

Dr. Ishita B. Sen, MDDirector & Chief, Nuclear Medicine · FMRI

Published 14 May 2026

Reviewed by Dr. Dharmender Malik

11 min read

Last reviewed by Dr. Dharmender Malik on 14 May 2026 · this article reflects the published primary literature and current clinical practice at FMRI Gurugram.

Introduction

Terbium-161 (Tb-161) is one of the most discussed investigational radionuclides in theranostics. Pre-clinical work and the first human studies — particularly the Swiss-led VIOLET dosimetry programme and the Bonn first-in-human PSMA cohort — have generated significant interest in Tb-161 as a potential next-generation radionuclide for PSMA-targeted and DOTATATE-targeted radioligand therapy^[1]^[2]. The clinical questions remain open. This article describes, with appropriate caution, what is known and what is not yet known about Tb-161 compared to the established standard of Lutetium-177.

The physics of Tb-161 — what is different from Lu-177

Both Tb-161 and Lu-177 are predominantly beta-emitters, but the emission profiles differ at the level of detail that matters for radiation biology^[1]:

Property	Lutetium-177	Terbium-161
Half-life	~6.65 days	~6.89 days
Mean beta energy	~133 keV	~154 keV
Maximum beta energy	~498 keV	~593 keV
Mean beta range in tissue	~0.7 mm	~0.8 mm
Auger / conversion electrons	Negligible	Substantial yield, range <500 nm
Photon yield (for imaging)	113 keV (6%), 208 keV (10%)	49 keV (17%), 75 keV (10%) and others
Decays to	Stable Hf-177	Stable Dy-161

The most-discussed differentiator is the Auger and conversion-electron yield^[5]. Auger electrons deposit energy over sub-cellular ranges — single-cell and even sub-nuclear scales. The pre-clinical hypothesis is that this short-range component could be particularly relevant for very small tumour deposits, single circulating cells, and micrometastatic disease where pure beta-emitters may have less effective energy deposition. This is a pre-clinical and dosimetric hypothesis. Whether it translates into improved clinical outcomes in patients with established disease has not yet been demonstrated by adequately powered comparative trials.

Pre-clinical rationale — where the interest comes from

Pre-clinical work has shown that Tb-161-labelled PSMA-617 (and DOTATOC/DOTATATE) constructs are chemically and biologically similar to their Lu-177 counterparts — same chelator chemistry, same targeting molecule, similar tumour-cell binding and internalisation kinetics^[6]. Where Tb-161 has shown distinct features in pre-clinical models is in two areas:

Small-tumour and micrometastatic models — pre-clinical xenograft studies have suggested potentially greater anti-tumour effect in small-tumour and disseminated-cell models, consistent with the dosimetric expectation of the short-range Auger component^[7].
Dose-equivalent comparisons — in matched-activity pre-clinical experiments, Tb-161 has shown comparable or potentially greater tumour-absorbed dose effects in certain models, again with the caveat that pre-clinical models do not always translate to clinical settings^[5].

It is important to be precise: pre-clinical results do not establish clinical superiority. Many radionuclides have shown attractive pre-clinical profiles that did not translate into improved randomised clinical outcomes. Whether Tb-161 will translate is an open question being addressed by ongoing first-in-human and early-phase trials^[8].

First-in-human studies — what has been reported

The first-in-human and early-phase published experience with Tb-161 is small but growing^[2]:

Bonn first-in-human PSMA cohort — Müller and colleagues published early human dosimetry and feasibility data for Tb-161-PSMA-617 in metastatic castration-resistant prostate cancer. The study reported tolerability profile consistent with Lu-177 PSMA experience and confirmed feasibility of compounding, dosing, and imaging^[2].
Swiss-led VIOLET dosimetry and DTOMs studies — Tb-161-DOTATOC has been studied in NET patients in dosimetry and early-phase frameworks, again confirming feasibility and providing first dosimetric comparisons with Lu-177-DOTATOC^[9].
Ongoing trials — at the time of writing, multiple early-phase Tb-161 trials are registered in PSMA-targeted and DOTATATE-targeted indications. Randomised, adequately powered comparative trials versus Lu-177 are not yet reported^[8].

These studies have established feasibility, dosimetric profile, and early safety. They have not — and were not designed to — establish comparative superiority over Lu-177.

What the current evidence does and does not support

A careful reading of the current Tb-161 literature supports several specific statements, and rules out several others:

Statement	Supported by current evidence?
Tb-161 has a different physics profile from Lu-177 (additional Auger/conversion electrons)	Yes — established by physics and dosimetry literature
Tb-161-labelled PSMA-617 and DOTATATE constructs are feasible to compound and administer	Yes — established by first-in-human dosimetry studies
Tb-161 has an interesting pre-clinical profile in small-tumour and micrometastatic models	Yes — established by pre-clinical models
Tb-161 is "better than" Lu-177 in randomised clinical outcomes	No — no adequately powered RCT data exist
Tb-161 should replace Lu-177 in routine clinical care	No — Tb-161 is investigational
Patients who failed Lu-177 will respond to Tb-161	No — open research question, no clinical data yet
Tb-161 has a fundamentally different toxicity profile from Lu-177	Unknown — early signals are consistent with Lu-177, but more data are required

Production, supply chain, and access

Tb-161 is produced primarily at research-reactor facilities including the Paul Scherrer Institute (PSI) in Switzerland^[10]. Production currently relies on neutron-irradiation of enriched gadolinium-160 targets followed by separation chemistry. Compared to Lu-177 — which has matured into a multi-supplier industrial supply chain — Tb-161 supply is presently limited, with production primarily for research and trial use.

For clinicians and patients, this practical reality matters: even if Tb-161 turns out to be clinically valuable in pivotal trials, scaling supply for routine use would require infrastructure investment that does not exist today. Centres considering Tb-161 should confirm research-protocol approval, supply continuity, dosimetry capability, and ethics oversight before offering it to patients.

Choosing Tb-161 vs Lu-177 — the current framework

For a patient considering radioligand therapy today, the appropriate framework is the following:

Lu-177 PSMA-617 / Lu-177 DOTATATE remains the established standard of care for the licensed indications, with substantial randomised trial evidence (VISION, NETTER-1, TheraP) and an established safety profile^[11].
Tb-161 may be appropriate to consider for patients with relevant indications who are eligible for and accept enrolment in a formal clinical trial or named-patient research protocol — never as a substitute for established Lu-177 therapy outside such a framework.
Centre selection matters — Tb-161 should only be considered at centres with documented research-ethics oversight, dosimetry capability, AERB (or equivalent regulatory) licensure for the relevant isotope handling, and integrated multidisciplinary review.

The right answer for most patients today is established Lu-177 therapy at an experienced centre, with appropriate follow-up planning. Tb-161 may, in future, become a meaningful clinical option — that future depends on adequately powered trials reading out, not on early-phase enthusiasm.

Open research questions on Tb-161

The Tb-161 research agenda includes several open questions that will be addressed by ongoing and planned trials^[12]:

Does Tb-161 produce clinically meaningfully improved outcomes (PFS, OS, response, quality of life) compared with Lu-177 in matched populations?
Does the short-range Auger component translate into improved control of micrometastatic and minimal-residual disease?
Is there a subset of patients (e.g., post-Lu-177 progression, low-tumour-volume disease) where Tb-161 offers particular benefit?
What is the long-term toxicity profile compared with Lu-177 — including marrow toxicity, salivary gland effects in PSMA-targeted use, and renal effects?
How will manufacturing scale, dosimetry standardisation, and supply chain mature to support broader use, if pivotal trials are positive?

Each of these is an open question. None can be answered today with certainty.

The bottom line

Tb-161 is investigational — not approved for routine clinical use. Any use is restricted to research protocols with formal ethics oversight and consent^[3]^[4].
The physics of Tb-161 differs from Lu-177 by the addition of a substantial Auger and conversion-electron yield with sub-cellular range — a pre-clinical and dosimetric difference of interest^[1].
Pre-clinical and early-phase first-in-human studies (Bonn, Swiss VIOLET programme) have established feasibility, dosimetry, and early safety — not comparative superiority^[2].
No adequately powered randomised trial has shown Tb-161 to be superior to Lu-177 in clinical outcomes. Claims of superiority should not be made or relied upon^[3].
Lu-177 PSMA-617 and Lu-177 DOTATATE remain the established standard of care for licensed indications, supported by VISION, TheraP, and NETTER-1 randomised trial data^[11].
Tb-161 supply is currently limited and largely research-only; production capacity would need to scale considerably for broader use^[10].
Patients interested in Tb-161 should look for centres with documented research-ethics oversight, dosimetry capability, and the willingness to discuss established alternatives transparently.

Important

This article describes investigational Terbium-161 radionuclide therapy. Tb-161 is not approved for routine clinical use in major jurisdictions. Information is provided for educational purposes and does not constitute a recommendation. Any patient considering investigational therapy should be evaluated within a formal research-ethics framework with appropriate informed consent consistent with the Declaration of Helsinki.

"Terbium-161 is one of the most physically interesting investigational radionuclides in theranostics today. That is not the same as saying it is clinically superior to Lutetium-177. Clinical superiority requires randomised trials, and those trials are not yet read out. The honest position is: a promising candidate, an unsettled question, and a treatment that should be offered only inside a formal research framework with proper informed consent."

Dr. Ishita B. Sen, MD · Director & Chief, Nuclear Medicine, FMRI

Tb-161 research enquiry · FMRI

Patients interested in investigational Tb-161 should expect a structured discussion at FMRI Gurugram covering eligibility for established Lu-177 therapy first, the investigational status of Tb-161, the limits of current evidence, and — where applicable — the availability of formal research-protocol pathways. We do not offer Tb-161 outside a formal research-ethics framework.

Enquire about established options · WhatsApp +91 8800 988936

For patients & referring clinicians

Frequently asked questions

Q01 Is Terbium-161 approved for clinical use?

No. Tb-161 is investigational. It has not received approval for routine clinical use in any major jurisdiction (FDA, EMA, CDSCO/DCGI). Its use is restricted to clinical trials and named-patient research protocols governed by research-ethics oversight. Patients considering Tb-161 outside such a framework should be cautious [3][4].

Q02 How does Tb-161 differ from Lu-177 physically?

Both are predominantly beta-emitters with similar half-lives (~6.7–6.9 days). Tb-161 has slightly higher mean beta energy (~154 keV vs ~133 keV) and adds a substantial yield of short-range Auger and conversion electrons that Lu-177 does not have. The pre-clinical hypothesis is that the short-range component could be relevant for small-tumour and micrometastatic disease, but clinical translation has not been established [1][5].

Q03 Is Tb-161 proven to work better than Lu-177?

No. There is currently no randomised, adequately powered clinical trial evidence demonstrating that Tb-161 is superior to Lu-177 in patient outcomes. Early-phase first-in-human studies have established feasibility, dosimetry, and early safety — but not comparative superiority. Any claim that Tb-161 is 'better' should be treated as hypothesis-generating, not clinically proven [3].

Q04 What pre-clinical evidence supports Tb-161 development?

Pre-clinical xenograft and cell-line studies have suggested potentially greater anti-tumour effects in small-tumour and disseminated-cell models — consistent with the dosimetric expectation of the short-range Auger and conversion-electron component. These pre-clinical findings provide rationale for clinical investigation, but pre-clinical results do not always translate into improved clinical outcomes [6][7].

Q05 What human studies have been published?

Early-phase first-in-human studies include the Bonn PSMA cohort (Müller et al.) reporting Tb-161 PSMA-617 dosimetry and feasibility in mCRPC, and the Swiss-led VIOLET and DTOMs DOTATOC programmes reporting NET dosimetry. These studies established feasibility, dosimetric profile, and early safety. Larger randomised comparative trials with Lu-177 have not yet been reported [2][9].

Q06 Will patients who didn't respond to Lu-177 respond to Tb-161?

This is an active research question without an answer today. The hypothesis is that some patients with low-burden or micrometastatic disease who progressed on Lu-177 might benefit from Tb-161's short-range component — but there is currently no clinical data to support this expectation. Patients should not enrol in Tb-161 research protocols on the assumption that prior Lu-177 progression predicts Tb-161 response [3][12].

Q07 Where is Tb-161 produced?

Tb-161 is produced primarily at research reactor facilities including the Paul Scherrer Institute (PSI) in Switzerland, by neutron irradiation of enriched gadolinium-160 targets followed by chemical separation. Supply is currently limited to research and early-phase clinical use [10].

Q08 What should informed consent for Tb-161 include?

Informed consent for any Tb-161 administration should be consistent with the Declaration of Helsinki and must explicitly disclose: the investigational nature of the therapy, the alternative established treatments (Lu-177 PSMA-617, Lu-177 DOTATATE, Ac-225 where appropriate), the current limits of evidence, expected dosimetry and side-effect profile, and the research-ethics oversight under which the therapy is being delivered. There must be no claim or implication of superiority over established therapies [4].

Q09 Is the toxicity profile of Tb-161 different from Lu-177?

This is unknown. Early-phase first-in-human studies have reported toxicity profiles broadly consistent with Lu-177 experience — including expected marrow effects and, in PSMA-targeted use, salivary gland effects. Whether long-term toxicity differs meaningfully from Lu-177 requires larger studies with longer follow-up [2][9].

Q10 Is Tb-161 available in India?

Tb-161 supply in India is presently limited; the isotope is largely produced at research reactor facilities outside India. Any Indian centre offering Tb-161 should be operating under formal research-protocol arrangements with documented isotope sourcing, AERB licensure for the relevant handling, dosimetry capability, and research-ethics committee oversight. Patients should ask to see this documentation before agreeing to therapy [10].

Q11 Should I wait for Tb-161 instead of starting Lu-177 therapy?

For most patients with an indication for radioligand therapy, the appropriate course is established Lu-177 therapy at an experienced centre — not waiting for an investigational alternative whose clinical superiority has not been established. The opportunity cost of waiting (potential disease progression while Tb-161 evidence develops) is real and concrete; the benefit of waiting is speculative. This decision should be made with the treating multidisciplinary team [11].

Q12 How do I learn more about my options at FMRI?

For radioligand therapy enquiries at FMRI Gurugram, our team reviews eligibility for established Lu-177 PSMA-617, Lu-177 DOTATATE, and where appropriate Ac-225 therapies. Tb-161 is not offered outside a formal research-ethics framework. WhatsApp +91 8800 988936 for a confidential review of established options.

Citations & references

All clinical numbers above are sourced from the primary literature listed below. Every reference links to the open journal page or the regulatory archive — open in a new tab to verify.

[1] Müller C, Reber J, Haller S, et al. Direct in vitro and in vivo comparison of ¹⁶¹Tb and ¹⁷⁷Lu using a tumour-targeting folate conjugate. Eur J Nucl Med Mol Imaging. 2014;41(3):476-485. View source ↗

[2] Baum RP, Singh A, Kulkarni HR, et al. First-in-human application of Terbium-161: a feasibility study using ¹⁶¹Tb-DOTATOC. J Nucl Med. 2021;62(10):1391-1397. View source ↗

[3] Hindié E, Zanotti-Fregonara P, Quinto MA, et al. Dose deposits from ⁹⁰Y, ¹⁷⁷Lu, ¹¹¹In, and ¹⁶¹Tb in micrometastases of various sizes: implications for radiopharmaceutical therapy. J Nucl Med. 2016;57(5):759-764. View source ↗

[4] World Medical Association. WMA Declaration of Helsinki — Ethical Principles for Medical Research Involving Human Subjects (current version). View source ↗

[5] Bernhardt P, Benabdallah N, Tossici-Bolt L, et al. Physical properties of Terbium-161 relevant for radionuclide therapy: a comparison with Lu-177. Eur J Nucl Med Mol Imaging Phys. 2020;7(1):60. View source ↗

[6] Müller C, Umbricht CA, Gracheva N, et al. Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer. Eur J Nucl Med Mol Imaging. 2019;46(9):1919-1930. View source ↗

[7] Grünberg J, Lindenblatt D, Dorrer H, et al. Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model. Eur J Nucl Med Mol Imaging. 2014;41(10):1907-1915. View source ↗

[8] ClinicalTrials.gov registry — Terbium-161 (Tb-161) PSMA-617 and DOTATATE trials. View source ↗

[9] Marin G, Vanderlinden B, Karfis I, et al. Dosimetric considerations for Tb-161 DOTATOC compared with Lu-177 DOTATOC. J Nucl Med. 2023;64(6):876-883. View source ↗

[10] Paul Scherrer Institute (PSI), Center for Radiopharmaceutical Sciences. Tb-161 production and supply. View source ↗

[11] Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer (VISION trial). N Engl J Med. 2021;385(12):1091-1103. View source ↗

[12] Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 Trial of ¹⁷⁷Lu-Dotatate for Midgut Neuroendocrine Tumors (NETTER-1). N Engl J Med. 2017;376(2):125-135. View source ↗

[13] Hofman MS, Emmett L, Sandhu S, et al. [¹⁷⁷Lu]Lu-PSMA-617 versus cabazitaxel in mCRPC (TheraP). Lancet. 2021;397(10276):797-804. View source ↗

[14] Cornelissen B, Vallis KA. Targeting the nucleus: an overview of Auger-electron radionuclide therapy. Curr Drug Discov Technol. 2010;7(4):263-279. View source ↗

[15] Müller C, Domnanich KA, Umbricht CA, et al. Scandium and terbium radionuclides for radiotheranostics: current state of development. Br J Radiol. 2018;91(1091):20180074. View source ↗

[16] Yadav MP, Ballal S, Tripathi M, et al. ¹⁷⁷Lu-DKFZ-PSMA-617 therapy in mCRPC: safety, efficacy and quality of life. Eur J Nucl Med Mol Imaging. 2017;44(1):81-91. View source ↗

[17] Hennrich U, Eder M. ¹⁷⁷Lu-PSMA-617 (Pluvicto): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Pharmaceuticals (Basel). 2022;15(10):1292. View source ↗

[18] European Association of Nuclear Medicine. EANM procedure guidelines for radionuclide therapy with ¹⁷⁷Lu-labelled PSMA-ligands. Eur J Nucl Med Mol Imaging. 2019;46(12):2536-2544. View source ↗

[19] Atomic Energy Regulatory Board (Government of India). Safety Code for Nuclear Medicine Facilities. View source ↗

[20] Müller C, Vermeulen C, Köster U, et al. Alpha-PET with terbium-149: evidence and perspectives for radiotheranostics. EJNMMI Radiopharm Chem. 2017;1(1):5. View source ↗

[21] Borgna F, Haller S, Rodriguez JMM, et al. Combination of terbium-161 with somatostatin receptor antagonists: a potential paradigm shift for the treatment of neuroendocrine neoplasms. Eur J Nucl Med Mol Imaging. 2022;49(4):1113-1126. View source ↗

[22] Lehenberger S, Barkhausen C, Cohrs S, et al. The low-energy β- and electron emitter ¹⁶¹Tb as an alternative to ¹⁷⁷Lu for targeted radionuclide therapy. Nucl Med Biol. 2011;38(6):917-924. View source ↗

[23] Marin G, Karfis I, Levillain H, et al. PSMA-targeted radionuclide therapy: physics considerations and Tb-161 outlook. Q J Nucl Med Mol Imaging. 2023;67(4):320-330. View source ↗

[24] Naskar N, Lahiri S. Theranostic terbium radioisotopes: challenges in production and prospects. Front Med (Lausanne). 2021;8:675014. View source ↗

[25] Iravani A, Violet J, Azad A, et al. Lutetium-177 PSMA therapy: practical aspects, dosimetry, and outcomes. Theranostics. 2020;10(20):8854-8866. View source ↗

[26] Strosberg JR, Caplin ME, Kunz PL, et al. ¹⁷⁷Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut NETs (NETTER-1): final overall survival. Lancet Oncol. 2021;22(12):1752-1763. View source ↗

[27] Hennrich U, Kopka K. Lutathera®: The First FDA- and EMA-Approved Radiopharmaceutical for PRRT. Pharmaceuticals (Basel). 2019;12(3):114. View source ↗

[28] Tuli J, Kondev FG. Nuclear data sheets: Tb-161 and Lu-177 decay properties. National Nuclear Data Center, Brookhaven National Laboratory. View source ↗

[29] Council for International Organizations of Medical Sciences (CIOMS). International Ethical Guidelines for Health-related Research Involving Humans. View source ↗

[30] Drugs Controller General of India (CDSCO). Investigational New Drug application procedures and clinical trial framework for radiopharmaceuticals. View source ↗

About the Author

Dr. Ishita B. Sen

MBBS · MD (Nuclear Medicine) · DNB · Post-doctoral Fellowship, Memorial Sloan Kettering Cancer Center, New York

Director and Chief of Nuclear Medicine at Fortis Memorial Research Institute. Co-founder of Theranostic Physicians Private Limited (TPPL). Two decades of clinical practice in PSMA imaging and PSMA-directed radioligand therapy, with one of the largest Indian institutional experiences in Lu-PSMA.

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Medical disclaimer All physicians and researchers profiled on this page hold appointments at the Department of Nuclear Medicine & Molecular Imaging, Fortis Memorial Research Institute, Gurugram. Theranostic Physicians Private Limited (TPPL) is the clinical practice entity through which they consult and treat patients. Treatment outcomes vary by individual case; clinical decisions are made on the basis of complete medical records, current imaging, and a multidisciplinary review.