Higher Efficacy & lower toxicity with Terbium-161

Terbium-161 Delivers More Precision with Less Toxicity Compared to Lu-177

Terbium-161 (Tb-161) is emerging as a superior alternative to Lutetium-177 (Lu-177) in radioligand therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). The ongoing VIOLET trial (ClinicalTrials.gov ID: NCT05521412) is evaluating [161Tb]Tb-PSMA-I&T as a next-generation therapeutic, and early findings support its higher efficacy and safer toxicity profile compared to Lu-177.

Lu-177 emits beta particles with a mean pathlength of about 0.7 mm. While effective against larger tumor masses, its limited energy range often fails to adequately irradiate micrometastases or single tumor cells, which are critical drivers of cancer progression. In contrast, Tb-161 emits not just beta particles but also Auger and conversion electrons, which deliver high-energy radiation over nanometer to micrometer distances—precisely where micrometastases reside.

As outlined in the VIOLET trial protocol published in the Journal of Nuclear Medicine
(https://doi.org/10.2967/jnumed.124.267650), 

Tb-161 results in approximately 35–40% more absorbed energy per decay than Lu-177. Importantly, this energy is more concentrated in the cancer cells without increasing the radiation burden to healthy tissues like the salivary glands or kidneys.

The VIOLET trial also applies advanced SPECT/CT-based dosimetry to validate that the actual tumor receives a higher radiation dose with Tb-161, while maintaining safety thresholds in normal organs. So far, early data confirm that Tb-161 has not introduced any unexpected toxicity and is well tolerated by patients.

Overall, Tb-161 delivers more radiation where it matters and less where it doesn’t, making it a promising candidate for more effective and safer treatment in advanced prostate cancer.

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