Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, E01,132, 3584 CX Utrecht, The Netherlands.
J Exp Clin Cancer Res. 2010 Jun 15;29(1):70. doi: 10.1186/1756-9966-29-70.
Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( 166Ho-PLLA-MS) have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of 166Ho-PLLA-MS radioembolization ( 166Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of 166Ho-RE in patients with liver metastases.
The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA) dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution.
This will be the first clinical study on 166Ho-RE. Based on preclinical studies, it is expected that 166Ho-RE has a safety and toxicity profile comparable to that of 90Y-RE. The biochemical and radionuclide characteristics of 166Ho-PLLA-MS that enable accurate dosimetry calculations and biodistribution assessment may however improve the overall safety of the procedure.
钇-90 微球（ 90Y-RE）的动脉内放射性栓塞治疗是一种越来越多用于治疗不可切除的肝脏恶性肿瘤的方法。在过去的十年中，放射性钬-166 聚（L-乳酸）微球（ 166Ho-PLLA-MS）已被开发为 90Y-RE 的可能替代物。除了高能β射线外， 166Ho 还发射γ射线，这使得可以通过伽马闪烁照相术进行成像。此外，Ho 是一种高顺磁性元素，因此可以通过 MRI 进行可视化。这些成像方式可用于评估生物分布，并通过对闪烁照相术和磁共振图像的定量分析来进行剂量测定。先前的研究已经证明了动物中 166Ho-PLLA-MS 放射性栓塞治疗（ 166Ho-RE）的安全性。本阶段 I 试验的目的是评估 166Ho-RE 在肝脏转移患者中的安全性和毒性概况。
HEPAR 研究（钬栓塞颗粒用于动脉放射治疗）是一项非随机、开放标签、安全性研究。我们的目标是纳入 15 至 24 名患有任何来源的肝脏转移瘤、化疗耐药且不适宜手术切除的患者。在治疗前，除了标准的锝-99m 标记的大聚合白蛋白（ 99mTc-MAA）剂量外，还将给予低放射性安全剂量 60 毫克 166Ho-PLLA-MS。根据标准剂量递增方案（分别为 20 Gy、40 Gy、60 Gy 和 80 Gy），将患者分为 4 组，每组 3-6 名患者。主要目标是确定 166Ho-PLLA-MS 的最大耐受辐射剂量。次要目标是评估肿瘤反应、生物分布、表现状态、生活质量，并比较 166Ho-PLLA-MS 安全剂量和 99mTc-MAA 剂量分布，以评估准确预测微球分布的能力。
这将是关于 166Ho-RE 的首个临床研究。基于临床前研究，预计 166Ho-RE 的安全性和毒性概况与 90Y-RE 相当。166Ho-PLLA-MS 的生化和放射性核素特性可实现准确的剂量计算和生物分布评估，从而可能提高该治疗过程的总体安全性。
