Terbium-161: A New Frontier in Targeted Radionuclide Therapy
Introduction
Recent advances in nuclear medicine are shining a spotlight on a promising new player: Terbium‑161 (¹⁶¹Tb). Long used radionuclides continue to form the backbone of targeted therapy, yet ¹⁶¹Tb brings a unique combination of physical properties — particularly the emission of short-ranged conversion and Auger electrons alongside traditional beta and gamma radiation — that might significantly enhance the effectiveness of treating microscopic disease and small metastases that often evade detection. Isotopia+2Journal of Nuclear Medicine+2
Where conventional radionuclides sometimes falter in eradicating minimal residual disease or tiny clusters of cancer cells, ¹⁶¹Tb may open the door to improved outcomes thanks to higher-density, localized radiation.
Why Terbium-161 Stands Out
• Radiobiological Advantages
Compared with the widely used Lutetium‑177 (¹⁷⁷Lu), ¹⁶¹Tb shares a similar half-life and decay scheme (beta emissions, gamma emissions suitable for imaging), making it relatively straightforward to integrate into existing radiopharmaceutical designs. PMC+2SpringerLink+2
However, the real distinction lies in the additional conversion and Auger electrons emitted by ¹⁶¹Tb after beta decay. These electrons have a very short range (on the order of 0.5–30 µm), allowing highly localized deposition of energy — ideal for destroying single tumor cells or small micrometastases while sparing surrounding healthy tissue. Isotopia+2Journal of Nuclear Medicine+2
Dosimetric comparisons show that for small volumes (10–100 µm), ¹⁶¹Tb can deliver 2–3 times higher energy transfer than ¹⁷⁷Lu, potentially translating into greater antitumour efficacy where small cell clusters or single-cell disease are involved. Isotopia+2Journal of Nuclear Medicine+2
• Versatile “Theranostic” Potential
Because ¹⁶¹Tb emits gamma rays as well as beta and Auger electrons, it can — in principle — be used for both therapy and imaging (SPECT), similar to existing theranostic pairings. PMC+2Frontiers+2
In practice, this dual role could simplify treatment workflows: the same molecular targeting agent (e.g. a peptide or ligand) labeled with ¹⁶¹Tb might first be used to image tumour distribution and dosimetry, then to deliver therapeutic radiation — enhancing personalization of radionuclide therapy. Frontiers+2SpringerLink+2
• Broad Applications — From Solid Tumours to Hematologic Malignancies
Initial research and clinical application have focused heavily on solid tumours — for instance, neuroendocrine tumours and prostate cancer — but the scope is expanding. Recent preclinical studies show that ¹⁶¹Tb-based radioimmunotherapy may also be effective against CD30-positive T-cell lymphomas, opening the door toward hematologic cancer applications. Journal of Nuclear Medicine+1
Moreover, because of its efficacy against small-volume disease — including circulating tumour cells and micrometastases — ¹⁶¹Tb may play a critical role in treating minimal residual disease, reducing relapse risk after standard therapies. Journal of Nuclear Medicine+2Nuclear Medicine Therapy+2
Progress & Challenges
Promising Clinical Data
One of the most significant developments occurred in 2025 with the first-in-human use of ¹⁶¹Tb-labeled radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC) — namely ¹⁶¹Tb-PSMA-I&T therapy. In a phase I/II clinical trial, doses up to 7.4 GBq were administered and the treatment was well tolerated, with only a minority of patients experiencing grade 3–4 adverse events. UroToday+2PubMed+2
Early efficacy signals have also been encouraging: a substantial proportion of patients experienced major declines in prostate-specific antigen (PSA) levels — a biomarker of disease burden — suggesting that ¹⁶¹Tb therapy can effectively reduce tumour load. UroToday+2UroToday+2
Preclinical data further supports superior potency of ¹⁶¹Tb over ¹⁷⁷Lu: in vitro studies reported multiple-fold stronger reduction in tumour cell viability with ¹⁶¹Tb-labeled compounds. Journal of Nuclear Medicine+2PMC+2
Manufacturing and Practical Challenges
Despite the promise, there remain non-trivial hurdles before ¹⁶¹Tb can become a mainstream therapeutic radionuclide. The main challenge lies in production at sufficient scale — neutron irradiation of highly enriched ^160Gd targets currently seems the most viable route, but achieving large-scale yields with consistent purity and specific activity is technically demanding. Isotopia+2National Isotope Development Center+2
Moreover, low-energy gamma emissions (e.g. ~49 keV, ~75 keV) pose challenges for imaging and dosimetry, particularly in standard clinical gamma cameras — requiring optimisation of imaging protocols or specialised equipment. SpringerLink+2PMC+2
Finally, compared with the decades of data accumulated for ¹⁷⁷Lu-based therapies, the body of clinical evidence for ¹⁶¹Tb remains relatively small. More clinical trials — including phase III studies — are needed to confirm long-term safety, optimal dosing, and effectiveness across diverse tumour types. ScienceDirect+2Open MedScience+2
What This Might Mean for Cancer Care
If ongoing clinical trials continue to show favourable safety and efficacy, ¹⁶¹Tb could reshape how we approach radionuclide therapy — especially with a shift toward treating minimal residual disease, early-stage micrometastasis, or single-cell clusters that are currently a major source of relapse.
Its “theranostic” nature — combining diagnostic imaging and therapy in one radionuclide — could streamline treatment planning, reduce patient burden, and help personalise therapy more precisely.
Furthermore, the versatility of ¹⁶¹Tb across different targeting moieties (e.g. PSMA ligands for prostate cancer; somatostatin analogues for neuroendocrine tumours; antibodies for lymphomas) creates the potential for broad application, beyond a single cancer type.
Conclusion
Targeted Radionuclide Therapy is growing increasingly sophisticated — and ¹⁶¹Tb may represent the next generation of radionuclides, combining proven beta and gamma emissions with the high-localised damage potential of conversion and Auger electrons.
While challenges remain — particularly in large-scale production and broader clinical validation — the early clinical and preclinical data are compelling. If these efforts bear out, ¹⁶¹Tb could become a powerful tool in the oncologist’s arsenal, especially when dealing with minimal residual disease or micrometastatic spread — key obstacles in achieving long-term remission.
In short: ¹⁶¹Tb doesn’t just promise a marginal improvement — it could redefine what we expect from radionuclide therapy.