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Purpose <p>Neuroblastoma frequently overexpresses somatostatin receptors (SSTR), enabling molecular radiotherapy with [<sup>177</sup>Lu]Lu-DOTATATE (<sup>177</sup>Lu-DOTATATE). Based on prior studies suggesting that dose intensification is required to achieve objective responses, the LuDO-N trial employs a two-fraction, high-activity treatment regimen. This study aimed to evaluate fraction-dependent changes in tumour and risk-organ absorbed doses, as well as the clinical safety of the intensified <sup>177</sup>Lu-DOTATATE treatment approach.</p> Methods <p>Fourteen patients with high-risk recurrent or refractory neuroblastoma received <sup>177</sup>Lu-DOTATATE in a dose-intensified, dosimetry-guided regimen. Treatment was given in two fractions 2–3 weeks apart, targeting a cumulative dose of either 2.4&#xa0;Gy to the whole body or 23&#xa0;Gy to either kidney. The first fraction was administered at 200 MBq/kg, while the second fraction was individually adjusted to achieve the dosimetric targets.</p> Results <p>Tumour-to-kidney and tumour-to-whole-body absorbed dose ratios both decreased significantly by 44% after the second fraction, compared to the first. Tumours received a median 53% lower absorbed dose per administered activity in the second fraction, while kidney and whole-body doses per activity were reduced by 24% and 18%, respectively. Four of fourteen patients (29%) underwent peripheral blood stem cell reinfusion. No sustained renal toxicity was observed.</p> Conclusions <p>These findings support a front-loaded <sup>177</sup>Lu-DOTATATE strategy to maximise tumour irradiation while maintaining exposure to risk organs within safety limits. Accordingly, the LuDO-N protocol has been amended to increase administered activity to 400 MBq/kg in the first fraction for subsequent patients. Together, this work contributes to the ongoing optimisation of dosimetry-guided and intensified treatment strategies for SSTR-targeted molecular radiotherapy for high-risk neuroblastoma.</p> Clinical trial registration <p>EU Clinical Trials Register, EU CT 2023-503684-42-00. Registered 2021-05-21.</p> <p><a href="https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en%26EUCT=2023-503684-42-00">https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&amp;EUCT=2023-503684-42-00</a>.</p>

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Fraction-dependent dose dynamics and clinical safety in high-risk neuroblastoma treated with [177Lu]Lu-DOTATATE: results from the LuDO-N trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Se Whee Sammy Park,
  • Fredrik Sundquist,
  • Leonor Teles,
  • Rob van Rooij,
  • Daniel Thor,
  • Kasper Karlsson,
  • Arthur J.A.T. Braat,
  • Jakob Stenman,
  • Joachim N. Nilsson

摘要

Purpose

Neuroblastoma frequently overexpresses somatostatin receptors (SSTR), enabling molecular radiotherapy with [177Lu]Lu-DOTATATE (177Lu-DOTATATE). Based on prior studies suggesting that dose intensification is required to achieve objective responses, the LuDO-N trial employs a two-fraction, high-activity treatment regimen. This study aimed to evaluate fraction-dependent changes in tumour and risk-organ absorbed doses, as well as the clinical safety of the intensified 177Lu-DOTATATE treatment approach.

Methods

Fourteen patients with high-risk recurrent or refractory neuroblastoma received 177Lu-DOTATATE in a dose-intensified, dosimetry-guided regimen. Treatment was given in two fractions 2–3 weeks apart, targeting a cumulative dose of either 2.4 Gy to the whole body or 23 Gy to either kidney. The first fraction was administered at 200 MBq/kg, while the second fraction was individually adjusted to achieve the dosimetric targets.

Results

Tumour-to-kidney and tumour-to-whole-body absorbed dose ratios both decreased significantly by 44% after the second fraction, compared to the first. Tumours received a median 53% lower absorbed dose per administered activity in the second fraction, while kidney and whole-body doses per activity were reduced by 24% and 18%, respectively. Four of fourteen patients (29%) underwent peripheral blood stem cell reinfusion. No sustained renal toxicity was observed.

Conclusions

These findings support a front-loaded 177Lu-DOTATATE strategy to maximise tumour irradiation while maintaining exposure to risk organs within safety limits. Accordingly, the LuDO-N protocol has been amended to increase administered activity to 400 MBq/kg in the first fraction for subsequent patients. Together, this work contributes to the ongoing optimisation of dosimetry-guided and intensified treatment strategies for SSTR-targeted molecular radiotherapy for high-risk neuroblastoma.

Clinical trial registration

EU Clinical Trials Register, EU CT 2023-503684-42-00. Registered 2021-05-21.

https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-503684-42-00.