# Peptide Receptor Radionuclide Therapy with Lu-177-DOTATATE and Monitoring with Somatostatin Receptor PET/CT in Patients with Advanced Differentiated Thyroid Carcinoma

**Authors:** Sophie Carina Kunte, Vera U. Wenter, Adrien Holzgreve, Gabriel T. Sheikh, Liam Widjaja, Franz Josef Gildehaus, Simon Lindner, Ralf Schirrmacher, Christine Spitzweg, Christoph J. Auernhammer, Rudolf A. Werner, Mathias J. Zacherl

PMC · DOI: 10.1007/s11307-025-02053-w · 2025-09-29

## TL;DR

This study explores the effectiveness of Lu-177-DOTATATE therapy in treating advanced thyroid cancer that no longer responds to traditional treatments.

## Contribution

The study evaluates PRRT in radioiodine-refractory differentiated thyroid carcinoma, a novel application of an established treatment.

## Key findings

- PRRT showed variable tumor control with no major side effects in advanced thyroid cancer patients.
- Discontinuous PRRT allowed for renewed tumor control upon reinitiation.
- SSTR PET/CT effectively identified eligible patients for PRRT.

## Abstract

Peptide receptor radionuclide therapy (PRRT) with Lu-177-DOTATATE is an established treatment option for neuroendocrine tumors (NETs) and has been extended to other somatostatin receptor (SSTR)-expressing tumors. We aimed to determine its efficacy and safety profile in patients with advanced radioiodine-refractory differentiated thyroid carcinoma (DTC).

Seven radioiodine-refractory DTC patients undergoing at least two cycles of PRRT were included. Patients were subdivided into continuous treatment (defined as sequential application of PRRT; 5/7 (71.4%)) vs. discontinuous treatment (with at least one-year PRRT-free interval; 2/7 (28.6%)). Baseline SSTR PET was analyzed to determine patients’ eligibility for PRRT. Response was assessed by tumor control as defined by stable (± 30.0%) or decreasing (≥ 30.0%) total tumor volume (PET-derived TTV), thyroglobulin (Tg) and RECIST 1.1 criteria.

SSTR PET showed discernible high uptake (maximum standardized uptake values, 10.4 ± 8.6) in metastases, in particular in the skeleton. Continuous PRRT showed variable tumor control (stable disease / response; TTV: 3/5 (60.0%); Tg: 2/5 (40.0%); RECIST 1.1: 3/5 (60.0%)). All patients undergoing discontinuous PRRT exhibited concordant stable disease upon first follow-up and renewed tumor control upon reinitiating PRRT (RECIST 1.1; decreasing TTV and Tg levels). No Common Terminology Criteria for Adverse Events (CTCAE) Grade 3–5 events occured in both groups.

In advanced radioiodine-refractory DTC, PRRT may be beneficial even after treatment interruptions, without major side effects. Given the small cohort and retrospective design, further prospective studies are needed to optimize PRRT strategies in DTC, in particular in a rechallenge scenario.

## Linked entities

- **Diseases:** differentiated thyroid carcinoma (MONDO:0015447)

## Full-text entities

- **Genes:** TG (thyroglobulin) [NCBI Gene 7038] {aka AITD3, TGN}
- **Diseases:** NETs (MESH:D018358), DTC (MESH:D013964), metastases (MESH:D009362), tumor (MESH:D009369)
- **Chemicals:** Lu-177-DOTATATE (-), radioiodine (MESH:C000614965)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12804201/full.md

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Source: https://tomesphere.com/paper/PMC12804201