# 161Tb-PSMA radioligand therapy in prostate cancer: current evidence and future perspectives

**Authors:** Liming Xiao, Ziyi Zhao, Rui Luo, Fucen Liu, Bosen Hu, Peng Zhao, Xia Yang, Zhengguo Chen

PMC · DOI: 10.3389/fonc.2025.1743628 · Frontiers in Oncology · 2026-01-14

## TL;DR

This paper reviews the potential of 161Tb-PSMA radioligand therapy for prostate cancer, highlighting its advantages over existing treatments and future research directions.

## Contribution

The paper introduces 161Tb as a promising alternative to 177Lu in PSMA-targeted radioligand therapy for prostate cancer.

## Key findings

- 161Tb emits β-particles, internal conversion, and Auger electrons, allowing effective targeting of small and large lesions.
- 161Tb-PSMA shows therapeutic promise in preclinical and clinical studies for metastatic castration-resistant prostate cancer.
- Further research is needed to validate the safety and efficacy of 161Tb-PSMA radioligand therapy.

## Abstract

Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein, is overexpressed on the membranes of prostate cancer cells. Lutetium-177 (177Lu)- labelled PSMA-targeted radioligand therapy (PRLT) is employed in treating metastatic castration-resistant prostate cancer (mCRPC) that no longer responds to conventional therapies. However, some patients develop resistance or exhibit limited responsiveness, resulting in disease progression. Terbium-161 (161Tb) shares physical properties with 177Lu, as both isotopes emit β- particles. Notably, 161Tb also emits internal conversion and Auger electrons, offering potential advantages in the effective targeting of small lesions. This dual-emission mechanism enables the treatment of lesions of varying sizes, generating growing interest in 161Tb-labelled radioligand therapy for prostate cancer. This review summarizes current evidence on 161Tb-PSMA, including its mechanism of action, radiolabeling and quality-control procedures, dosimetry, preclinical results, and clinical outcomes, highlighting its therapeutic promise. Future investigations should further validate the safety and efficacy of 161Tb-PSMA radioligand therapy, while enhancing its accessibility and clinical translation.

## Linked entities

- **Proteins:** FOLH1 (folate hydrolase 1)
- **Chemicals:** Lutetium-177 (PubChem CID 161046), Terbium-161 (PubChem CID 177426)
- **Diseases:** prostate cancer (MONDO:0005159)

## Full-text entities

- **Genes:** FOLH1 (folate hydrolase 1) [NCBI Gene 2346] {aka FGCP, FOLH, GCP2, GCPII, NAALAD1, PSM}
- **Diseases:** castration-resistant prostate cancer (MESH:D064129), prostate cancer (MESH:D011471)
- **Chemicals:** Terbium-161 (MESH:C000615038), 161Tb (-), 177Lu (MESH:C000615061)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12847022/full.md

## References

58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12847022/full.md

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Source: https://tomesphere.com/paper/PMC12847022