Validation of MRI quantitative susceptibility mapping of superparamagnetic iron oxide nanoparticles for hyperthermia applications in live subjects
Validation of MRI quantitative susceptibility mapping of superparamagnetic iron oxide nanoparticles for hyperthermia applications in live subjects
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DOI：
10.1038/s41598-020-58219-9
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发表时间：
2020-01-24
影响因子：
4.6
通讯作者：
Jin, Moonsoo M.
中科院分区：
文献类型：
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作者：
Deh, Kofi;Zaman, Marjan;Jin, Moonsoo M.
磁流体热疗（MFH）用于癌症治疗已经显示出前景，但缺乏合适的方法来量化外源性铁，如超顺磁性氧化铁（SPIO）纳米颗粒作为交变磁场（AMF）下发热的来源。由于敏感性值的巨大变化、组织脂肪的化学转移以及小动物解剖可视化所需的更高分辨率所产生的嘈杂数据，将定量敏感性制图（QSM）技术应用于临床前模型中SPIO的预测一直具有挑战性。在这项研究中，我们在活小鼠中建立了SPIO阿鲁莫糖醇的稳健QSM，以检验其在MFH中用于癌症治疗的潜在应用。我们证明，QSM能够同时检测肝脏中高水平的阿魏木醇积累和肿瘤周围低水平的定位。然而，通过QSM检测阿魏木糖醇在体内的分布，需要在阿魏木糖醇注射前后进行成像，以区分外源性铁敏感性和其他内源性铁敏感性。肿瘤内注射阿魏木糖醇联合AMF产生阿魏木糖醇剂量依赖性肿瘤杀伤作用。肿瘤切片组织学证实了QSM显示阿魏木糖醇在肿瘤周围分布，并证实了细胞死亡与阿魏木糖醇分布的空间相关性。由于SPIO从注射部位消散，定量绘制SPIO分布将有助于估计组织温度的变化，从而最大限度地发挥MFH对肿瘤的作用，并通过避免不必要的组织加热来最大限度地减少副作用。
The use of magnetic fluid hyperthermia (MFH) for cancer therapy has shown promise but lacks suitable methods for quantifying exogenous irons such as superparamagnetic iron oxide (SPIO) nanoparticles as a source of heat generation under an alternating magnetic field (AMF). Application of quantitative susceptibility mapping (QSM) technique to prediction of SPIO in preclinical models has been challenging due to a large variation of susceptibility values, chemical shift from tissue fat, and noisier data arising from the higher resolution required to visualize the anatomy of small animals. In this study, we developed a robust QSM for the SPIO ferumoxytol in live mice to examine its potential application in MFH for cancer therapy. We demonstrated that QSM was able to simultaneously detect high level ferumoxytol accumulation in the liver and low level localization near the periphery of tumors. Detection of ferumoxytol distribution in the body by QSM, however, required imaging prior to and post ferumoxytol injection to discriminate exogenous iron susceptibility from other endogenous sources. Intratumoral injection of ferumoxytol combined with AMF produced a ferumoxytol-dose dependent tumor killing. Histology of tumor sections corroborated QSM visualization of ferumoxytol distribution near the tumor periphery, and confirmed the spatial correlation of cell death with ferumoxytol distribution. Due to the dissipation of SPIOs from the injection site, quantitative mapping of SPIO distribution will aid in estimating a change in temperature in tissues, thereby maximizing MFH effects on tumors and minimizing side-effects by avoiding unwanted tissue heating.