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Theranostics — Lu-177 DOTATATE and Lu-177 PSMA
Theranostics means "see, then treat with the same key": imaging (Ga-68 or F-18) proves that the tumour expresses the target, then the isotope is swapped for a beta emitter (Lu-177) that irradiates the cells from within.
Why it matters in the exam
The exam asks about indications and pivotal trials. Lu-177 DOTATATE (PRRT): in NETTER-1 it improved progression-free survival in well-differentiated small-bowel tumours progressing on a somatostatin analogue; the usual protocol is 7.4 GBq every 8 weeks, 4 cycles. Lu-177 PSMA-617: in VISION it improved overall survival in metastatic castration-resistant prostate cancer (mCRPC) after new-generation hormonal therapy and after a taxane; 7.4 GBq every 6 weeks, up to 6 cycles. The condition for both: sufficient uptake in all significant lesions on imaging.
Lu-177 emits beta particles with a short tissue range (up to about 2 mm) and also gamma rays that allow the treatment distribution to be imaged. Its half-life is about 6.7 days. Y-90 emits higher-energy beta particles with a longer range (up to about 11 mm), so it has an advantage in large tumours with uneven expression ("crossfire effect"), but at the price of higher renal toxicity; Lu-177 is better for small lesions. In PRRT an amino acid infusion (lysine and arginine) is given to protect the kidneys, and it is the main cause of nausea.
Toxicity: marrow suppression (mainly platelets and lymphocytes), late renal injury, and in a small proportion (about 1%–2%) MDS or leukaemia. With PSMA — dry mouth from salivary gland uptake, fatigue and nausea. Relative contraindications: low blood counts, poor renal function, and in PSMA therapy — lesions that take up FDG but not PSMA. Radiation precautions: most treatments are given as a day case or short admission, with advice to drink plenty, to urinate sitting down and to keep distance from children and pregnant women for several days, and contraception for a set period. I-131 MIBG and Ra-223 are other radionuclide treatments, and I-131 is the oldest of all.
Key points
- Theranostics — imaging proves the target, then treatment with the same molecule.
- NETTER-1 — Lu-177 DOTATATE in progressing small-bowel NET.
- VISION — Lu-177 PSMA in mCRPC after new hormonal therapy and a taxane.
- Lu-177 — short-range beta and gamma for imaging; Y-90 — long range and renal toxicity.
- Toxicity: marrow, kidneys, dry mouth with PSMA.
Summary table
| Treatment | Indication | Activity and frequency | Main toxicity |
|---|---|---|---|
| Lu-177 DOTATATE | Progressing well-differentiated NET, SSTR-positive | 7.4 GBq every 8 weeks, 4 cycles | Marrow, kidneys, MDS |
| Lu-177 PSMA-617 | mCRPC after new hormonal therapy and taxane, PSMA-positive | 7.4 GBq every 6 weeks, up to 6 | Dry mouth, marrow |
| Y-90 DOTATOC | Large tumours | Centre-specific | Kidneys |
| I-131 MIBG | MIBG-avid phaeochromocytoma or neuroblastoma | Centre-specific | Marrow, thyroid |
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Sources
- Joint IAEA, EANM and SNMMI Practical Guidance on Peptide Receptor Radionuclide Therapy (PRRNT) in Neuroendocrine Tumours, 2013 — Patient selection, administration and toxicity
- EANM Procedure Guidelines for Radionuclide Therapy with Lu-177-labelled PSMA-ligands, 2023 — Indications, contraindications and follow-up
- Phase 3 Trials of Lu-177-DOTATATE (NETTER-1) and Lu-177-PSMA-617 (VISION), 2017 and 2021 — Eligibility and outcomes
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.