# Radioligand therapy

Source: https://nuclide.cc/fronts/f-radioligand-therapy/  
Nuclide record `f-radioligand-therapy` (Front). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Radioligand therapy attaches a radioactive particle to a molecule that homes in on a tumour, so the radiation is delivered from the inside of the cancer rather than from an external beam.

## Summary

Radioligand therapy (RLT) with beta-emitters is the most clinically mature branch of theranostics. Lutetium-177 vipivotide tetraxetan (Pluvicto, 177Lu-PSMA-617) is approved by the FDA and EMA for PSMA-positive metastatic castration-resistant prostate cancer, on the strength of the VISION trial (median overall survival 15.3 vs 11.3 months, HR 0.62; radiographic progression-free survival 8.7 vs 3.4 months, HR 0.40; Sartor et al., NEJM 2021) and the earlier-line PSMAfore trial (rPFS 9.3 vs 5.6 months, HR 0.41), which supported the FDA's March 2025 label expansion into taxane-naive mCRPC. Lutetium-177 dotatate (Lutathera) is approved for gastroenteropancreatic neuroendocrine tumours on the basis of NETTER-1 (Strosberg et al., NEJM 2017) and has since been extended to a first-line setting by NETTER-2 (Lancet 2024).

A competitive multi-agent PSMA-RLT field is emerging behind Pluvicto: 177Lu-PSMA-I&T (PNT2002, Lantheus/POINT Biopharma) reported the SPLASH trial, and Telix's antibody-based rosopatamab tetraxetan (TLX591-Tx) is in the ProstACT Global phase 3 programme. On the neuroendocrine side, 177Lu-edotreotide (ITM-11) and FAP-targeted 177Lu-FAP-2286 are in later-phase development.

What remains unsolved: a 2026 GRADE-assessed meta-analysis of six randomised trials (Mubarika et al., Int Urol Nephrol 2026) found the primary intention-to-treat overall-survival benefit of 177Lu-PSMA over standard of care was not statistically significant (HR 0.81, 95% CI 0.62-1.06), with a benefit only apparent after adjusting for control-arm crossover (HR 0.76, 95% CI 0.59-0.96) — a reminder that trial-design choices, not just the isotope, drive the reported benefit. Optimal sequencing against androgen-receptor pathway inhibitors, taxanes and alpha emitters is still being worked out in trials such as PSMAddition and ENZA-p, and lutetium-177's roughly 0.5-2 mm beta path length is thought to undertreat isolated tumour cells and micrometastases, motivating the move to alpha emitters.

## Fields

- Kind: Front
- Last checked: 2026-09-22

## Notes

- A 2026 GRADE meta-analysis found the ITT overall-survival benefit of 177Lu-PSMA vs standard of care was not significant (HR 0.81, 95% CI 0.62-1.06) until adjusted for crossover (HR 0.76, 95% CI 0.59-0.96); trial design materially changes the reported effect size.
- Optimal sequencing of RLT against ARPIs, taxanes and alpha emitters is unresolved; PSMAddition and ENZA-p are testing earlier and combined use.
- 177Lu's beta path length (roughly 0.5-2 mm) is thought to leave isolated tumour cells and micrometastases undertreated, which is the main argument for moving to alpha emitters.

## Sources

- FDA label: Pluvicto (accessdata.fda.gov): https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215833s000lbl.pdf
- VISION trial (Sartor et al., NEJM 2021): https://www.nejm.org/doi/10.1056/NEJMoa2107322
- GRADE-assessed meta-analysis of 177Lu-PSMA RCTs (Int Urol Nephrol, 2026): https://pubmed.ncbi.nlm.nih.gov/42570199/
- Guideline of guidelines: 177Lu-PSMA RLT (BJU Int, 2026): https://pmc.ncbi.nlm.nih.gov/articles/PMC13458634/

## Connected records

- fronts: [Bone-targeted radiopharmaceuticals](https://nuclide.cc/fronts/f-bone-targeted/), [Dosimetry](https://nuclide.cc/fronts/f-dosimetry/), [Isotope supply](https://nuclide.cc/fronts/f-isotope-supply/), [Molecular imaging](https://nuclide.cc/fronts/f-molecular-imaging/), [Targeted alpha therapy](https://nuclide.cc/fronts/f-alpha-therapy/)
- isotopes: [Lutetium-177](https://nuclide.cc/isotopes/lu-177/)
- indications: [Lung neuroendocrine tumours (typical and atypical carcinoid)](https://nuclide.cc/indications/lung-net/), [Metastatic castration-resistant prostate cancer](https://nuclide.cc/indications/prostate-mcrpc/), [Metastatic hormone-sensitive prostate cancer](https://nuclide.cc/indications/prostate-mhspc/), [Neuroendocrine tumours](https://nuclide.cc/indications/neuroendocrine/), [Pancreatic neuroendocrine tumours](https://nuclide.cc/indications/pancreatic-net/), [Small intestinal neuroendocrine tumours](https://nuclide.cc/indications/small-intestinal-net/)
- technologies: [Lutetium-177 radioligand therapy](https://nuclide.cc/technologies/lu177-radioligand-therapy/), [Peptide receptor radionuclide therapy (PRRT)](https://nuclide.cc/technologies/prrt/), [Peptide-drug & small-molecule-drug conjugates](https://nuclide.cc/technologies/peptide-drug-conjugate/), [PSMA PET](https://nuclide.cc/technologies/psma-pet/), [Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/), [Somatostatin receptor PET (68Ga/64Cu-DOTATATE)](https://nuclide.cc/technologies/sstr-pet/)
- drugs: [177Lu-edotreotide](https://nuclide.cc/drugs/itm-11/), [177Lu-PSMA-I&T](https://nuclide.cc/drugs/lu177-psma-it/), [FAP-2286 (177Lu / 68Ga)](https://nuclide.cc/drugs/fap-2286/), [Lutetium-177 dotatate](https://nuclide.cc/drugs/lutathera/), [Lutetium-177 vipivotide tetraxetan](https://nuclide.cc/drugs/pluvicto/)
- companies: [Advanced Accelerator Applications (Novartis)](https://nuclide.cc/companies/advanced-accelerator-applications/), [ITM Isotope Technologies Munich](https://nuclide.cc/companies/itm/), [Lantheus](https://nuclide.cc/companies/lantheus/), [Novartis](https://nuclide.cc/companies/novartis/), [POINT Biopharma](https://nuclide.cc/companies/point-biopharma/), [Telix Pharmaceuticals](https://nuclide.cc/companies/telix/)
- terms: [mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)](https://nuclide.cc/terms/mcrpc-mhspc/), [PRRT (peptide receptor radionuclide therapy)](https://nuclide.cc/terms/prrt-term/), [PSA50 / PSA90 response](https://nuclide.cc/terms/psa50/)
- trials: [NETTER-1](https://nuclide.cc/trials/netter-1/), [PSMAddition](https://nuclide.cc/trials/psmaddition/), [PSMAfore](https://nuclide.cc/trials/psmafore/), [SPLASH](https://nuclide.cc/trials/splash/), [VISION](https://nuclide.cc/trials/vision/)
- key papers: [NETTER-1: 177Lu-Dotatate for midgut neuroendocrine tumours progressing on octreotide](https://nuclide.cc/key-papers/paper-netter-1-nejm-2017/), [NETTER-2: lutetium-177 dotatate as first treatment for higher-grade gastroenteropancreatic neuroendocrine tumours](https://nuclide.cc/key-papers/paper-netter-2-lancet-2024/), [VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer](https://nuclide.cc/key-papers/paper-vision-nejm-2021/)

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