Brigham and Women's Hospital|Dana-Farber Cancer Institute|Harvard Medical School, Boston, MA, USA.
Université Grenoble Alpes, CHU Grenoble Alpes, Service de Radiothérapie, Inserm UA7, Grenoble, France.
Sci Rep. 2024 May 25;14(1):11959. doi: 10.1038/s41598-024-62389-1.
AGuIX, a novel gadolinium-based nanoparticle, has been deployed in a pioneering double-blinded Phase II clinical trial aiming to assess its efficacy in enhancing radiotherapy for tumor treatment. This paper moves towards this goal by analyzing AGuIX uptake patterns in 23 patients. A phantom was designed to establish the relationship between AGuIX concentration and longitudinal ( ) relaxation. A 3T MRI and MP2RAGE sequence were used to generate patient maps. AGuIX uptake in tumors was determined based on longitudinal relaxivity. AGuIX (or placebo) was administered to 23 patients intravenously at 100 mg/kg 1-5 hours pre-imaging. Each of 129 brain metastases across 23 patients were captured in maps and examined for AGuIX uptake and distribution. Inferred AGuIX recipients had average tumor uptakes between 0.012 and 0.17 mg/ml, with a mean of 0.055 mg/ml. Suspected placebo recipients appeared to have no appreciable uptake. Tumors presented with varying spatial AGuIX uptake distributions, suspected to be related to differences in accumulation time and patient-specific bioaccumulation factors. This research demonstrates AGuIX's ability to accumulate in brain metastases, with quantifiable uptake via mapping. Future analyses will extend these methods to complete clinical trial data (~ 134 patients) to evaluate the potential relationship between nanoparticle uptake and possible tumor response following radiotherapy.Clinical Trial Registration Number: NCT04899908.Clinical Trial Registration Date: 25/05/2021.
一种新型的基于镧系元素的纳米颗粒 AGuIX 已被用于一项开创性的、双盲的 II 期临床试验中,旨在评估其在增强肿瘤放射治疗方面的疗效。本文通过分析 23 名患者的 AGuIX 摄取模式来实现这一目标。设计了一个体模来建立 AGuIX 浓度与纵向弛豫时间( )之间的关系。使用 3T MRI 和 MP2RAGE 序列生成患者图谱。根据纵向弛豫率确定肿瘤内的 AGuIX 摄取量。将 23 名患者静脉内以 100mg/kg 的剂量在成像前 1-5 小时给予 AGuIX(或安慰剂)。对 23 名患者的 129 个脑转移瘤进行了 图谱采集,并检查了 AGuIX 的摄取和分布。推断的 AGuIX 接受者的肿瘤平均摄取量在 0.012 和 0.17mg/ml 之间,平均值为 0.055mg/ml。疑似安慰剂接受者似乎没有明显的摄取。肿瘤呈现出不同的 AGuIX 摄取分布空间,疑似与积累时间和患者特异性生物积累因素的差异有关。这项研究证明了 AGuIX 能够在脑转移瘤中积累,并通过 图谱进行可量化的摄取。未来的分析将扩展这些方法以包括完整的临床试验数据(~134 名患者),以评估纳米颗粒摄取与放疗后可能的肿瘤反应之间的潜在关系。临床试验注册号:NCT04899908.临床试验注册日期:2021 年 5 月 25 日。