Purpose

To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [¹⁷⁷Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs).

Methods

This study was part of a phase I/II trial of [¹⁷⁷Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.5 GBq), in 40 patients with progressive NETs. Organ absorbed doses were monitored at each cycle using patient-specific dosimetry; the cumulative absorbed-dose limits were set at 23.0 Gy for the kidneys and 1.5 Gy for bone marrow. Absorbed dose coefficients (ADCs) were calculated using both patient-specific and model-based dosimetry for some patients.

Results

In all evaluated organs, maximum [¹⁷⁷Lu]Lu-satoreotide tetraxetan uptake was observed at the first imaging timepoint (4 h after injection), followed by an exponential decrease. Kidneys were the main route of elimination, with a cumulative excretion of 57–66% within 48 h following the first treatment cycle. At the first treatment cycle, [¹⁷⁷Lu]Lu-satoreotide tetraxetan showed a median terminal blood half-life of 127 h and median ADCs of [¹⁷⁷Lu]Lu-satoreotide tetraxetan were 5.0 Gy/GBq in tumours, 0.1 Gy/GBq in the bone marrow, 0.9 Gy/GBq in kidneys, 0.2 Gy/GBq in the liver and 0.8 Gy/GBq in the spleen. Using image-based dosimetry, the bone marrow and kidneys received median cumulative absorbed doses of 1.1 and 10.8 Gy, respectively, after three cycles.

Conclusion

[¹⁷⁷Lu]Lu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy.

Trial registration

NCT02592707. Registered October 30, 2015.

中文翻译：

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[177Lu]Lu-satoreotide tetraxetan 在进行性神经内分泌肿瘤患者中的剂量测定和药代动力学

目的

评估新型放射性标记生长抑素受体拮抗剂[ ¹⁷⁷ Lu]Lu-satoreotide tetraxetan 在晚期神经内分泌肿瘤（NET）患者中的剂量测定和药代动力学。

方法

^{本研究是 [ 177} Lu]Lu-satoreotide tetraxetan的 I/II 期试验的一部分，在 40 名进行性 NET 患者中，在三个计划周期内以中位累积活性 13.0 GBq（中位活性/周期：4.5 GBq）进行给药。使用患者特异性剂量测定法在每个周期监测器官吸收剂量；肾脏的累积吸收剂量限值设定为 23.0 Gy，骨髓的累积吸收剂量限值设定为 1.5 Gy。对于某些患者，使用特定患者剂量测定法和基于模型的剂量测定法计算吸收剂量系数 (ADC)。

结果

在所有评估的器官中，在第一个成像时间点（注射后4小时）观察到最大[ ¹⁷⁷ Lu]Lu-satoreotide tetraxetan摄取，随后呈指数下降。肾脏是主要的消除途径，第一个治疗周期后48小时内累积排泄率为57-66%。在第一个治疗周期，[ ¹⁷⁷ Lu]Lu-satoreotide tetraxetan 显示中位终末血液半衰期为 127 小时，[ ¹⁷⁷ Lu]Lu-satoreotide tetraxetan 的中位 ADC 在肿瘤中为 5.0 Gy/GBq，在肿瘤中为 0.1 Gy/GBq。骨髓、肾脏 0.9 Gy/GBq、肝脏 0.2 Gy/GBq 和脾脏 0.8 Gy/GBq。使用基于图像的剂量测定，三个周期后，骨髓和肾脏分别接受了 1.1 和 10.8 Gy 的中位累积吸收剂量。

结论

[ ¹⁷⁷ Lu]Lu-satoreotide tetraxetan 显示出良好的剂量学特征，具有高且持久的肿瘤摄取，支持其可接受的安全性和有希望的疗效。

试用注册

NCT02592707。 2015年10月30日注册。