Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study
Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study
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DOI：
10.1158/1078-0432.ccr-16-1990
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发表时间：
2017-07-15
影响因子：
11.5
通讯作者：
Fitzgerald, Jonathan B.
中科院分区：
文献类型：
--
作者：
Ramanathan, Ramesh K.;Korn, Ronald L.;Fitzgerald, Jonathan B.
目的：为了确定通过定量MRI鉴定的肿瘤中ferumoxytol（FMX）铁纳米颗粒的沉积特征是否可以预测肿瘤病变对纳米脂质体伊立替康（nal-IRI）的反应，实验设计：具有先前治疗的实体瘤的合格患者在FMX注射之前和之后（1、24和72小时）进行FMX-MRI扫描。MRI采集后，通过与基于体模的标准曲线比较，使用R2* 信号计算血浆、参考组织和肿瘤病变中的FMX水平。然后患者接受nal-IRI（70 mg/m2游离碱强度），每两周一次，直至进展。两个经皮核心活检收集选定的肿瘤病变72小时后FMX或nal-IRI.Results：铁粒子水平定量FMX-MRI在血浆中，参考组织，和肿瘤病变在13 15个合格的患者。基于一个机械动力学模型，组织对FMX的渗透性与1和24小时的早期FMX-MRI信号相关，而FMX组织结合在72小时起作用。较高的FMX水平（相对于9例患者的多个可评估病灶的中位数进行排名）与早期时间点RECIST v1.1的病灶大小减小显著相关（1小时时P < 0.001，24小时时P < 0.003，单因素方差分析）。在72小时时未观察到与FMX后水平的相关性。病灶中伊立替康药物水平与患者治疗时间相关（斯皮尔曼r = 0.7824; P = 0.0016）。结论：肿瘤病灶中FMX水平与nal-IRI活性之间的相关性表明，病灶对FMX的渗透性和随后的肿瘤摄取可能是实体瘤患者nal-IRI反应的有用的非侵入性和预测性生物标志物。(C)2017年AACR。
Purpose: To determine whether deposition characteristics of ferumoxytol (FMX) iron nanoparticles in tumors, identified by quantitative MRI, may predict tumor lesion response to nanoliposomal irinotecan (nal-IRI).Experimental Design: Eligible patients with previously treated solid tumors had FMX-MRI scans before and following (1, 24, and 72 hours) FMX injection. After MRI acquisition, R2* signal was used to calculate FMX levels in plasma, reference tissue, and tumor lesions by comparison with a phantom-based standard curve. Patients then received nal-IRI (70 mg/m(2) free base strength) biweekly until progression. Two percutaneous core biopsies were collected from selected tumor lesions 72 hours after FMX or nal-IRI.Results: Iron particle levels were quantified by FMX-MRI in plasma, reference tissues, and tumor lesions in 13 of 15 eligible patients. On the basis of a mechanistic pharmacoki-netic model, tissue permeability to FMX correlated with early FMX-MRI signals at 1 and 24 hours, while FMX tissue binding contributed at 72 hours. Higher FMX levels (ranked relative to median value of multiple evaluable lesions from 9 patients) were significantly associated with reduction in lesion size by RECIST v1.1 at early time points (P < 0.001 at 1 hour and P < 0.003 at 24 hours FMX-MRI, one-way ANOVA). No association was observed with post-FMX levels at 72 hours. Irinotecan drug levels in lesions correlated with patient's time on treatment (Spearman r = 0.7824; P = 0.0016).Conclusions: Correlation between FMX levels in tumor lesions and nal-IRI activity suggests that lesion permeability to FMX and subsequent tumor uptake may be a useful noninvasive and predictive biomarker for nal-IRI response in patients with solid tumors. (C) 2017 AACR.