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

IF 7.6 1区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2026-09-01 Epub Date: 2026-06-19 DOI:10.1007/s00259-026-07984-2

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

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引用次数: 0

Abstract

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 .

查看原文本刊更多论文

[177Lu]Lu-DOTATATE治疗高危神经母细胞瘤的分数依赖剂量动力学和临床安全性：来自LuDO-N试验的结果。

目的：神经母细胞瘤经常过度表达生长抑素受体（SSTR），使得[177Lu]Lu-DOTATATE （177Lu- dotatate）分子放疗成为可能。基于先前的研究表明，剂量强化需要达到客观反应，LuDO-N试验采用了两部分，高活性的治疗方案。本研究旨在评估肿瘤和危险器官吸收剂量的分数依赖性变化，以及强化177Lu-DOTATATE治疗方法的临床安全性。方法：14例高风险复发或难治性神经母细胞瘤患者在剂量强化、剂量学指导的方案中接受177Lu-DOTATATE治疗。治疗分两部分进行，间隔2-3周，目标累积剂量为全身2.4 Gy或任一肾脏23 Gy。第一部分以200 MBq/kg的剂量给药，而第二部分则单独调整以达到剂量学目标。结果：与第一次相比，第二部分后肿瘤对肾脏和肿瘤对全身吸收剂量比均显著降低44%。在第二部分中，肿瘤的每次给药剂量中位数降低了53%，而肾脏和全身每次给药剂量分别降低了24%和18%。14例患者中有4例（29%）接受了外周血干细胞再输注。未观察到持续的肾毒性。结论：这些发现支持前置177Lu-DOTATATE策略，以最大化肿瘤照射，同时将暴露于危险器官的暴露保持在安全限度内。因此，修订了LuDO-N方案，将后续患者的第一部分给药活性提高到400 MBq/kg。总之，这项工作有助于持续优化剂量学指导和强化治疗策略，用于高危神经母细胞瘤的sstr靶向分子放疗。临床试验注册：EU临床试验注册，EU CT 2023-503684-42-00。注册2021-05-21。https://euclinicaltrials.eu/search - -临床trials/?lang=en&euct=2023 - 503684 - 42 - 00。

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来源期刊

European Journal of Nuclear Medicine and Molecular Imaging 医学-核医学

CiteScore

15.60

自引率

9.90%

发文量

392

审稿时长

3 months

期刊介绍： The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.