Nanoparticle Redistribution in PC3 Tumors Induced by Local Heating in Magnetic Nanoparticle Hyperthermia: In Vivo Experimental Study
Nanoparticle Redistribution in PC3 Tumors Induced by Local Heating in Magnetic Nanoparticle Hyperthermia: In Vivo Experimental Study
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DOI：
10.1115/1.4042298
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发表时间：
2019-03-01
影响因子：
--
通讯作者：
Zhu, Liang
中科院分区：
文献类型：
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作者：
Gu, Qimei;Joglekar, Tejashree;Zhu, Liang
在磁性纳米颗粒热疗中，破坏肿瘤所需的热剂量很大程度上取决于纳米颗粒在肿瘤中的分布。本研究的目的是进行体内实验，以评估使用磁性纳米粒子热疗进行局部加热是否会改变前列腺癌（PC3）肿瘤中的纳米粒子浓度分布。对植入小鼠体内的移植 PC3 肿瘤进行体内动物实验，研究通过将肿瘤暴露于交变磁场（5 kA/m 和 192 kHz）25 分钟进行局部加热是否导致纳米颗粒从肿瘤内注射部位扩散到肿瘤周围。通过将加热后切除肿瘤的 microCT 图像与未加热的对照组的图像进行比较，评估局部加热引起的纳米颗粒重新分布。先前确定的 microCT 亨斯菲尔德单位 (HU) 值与肿瘤中局部纳米颗粒浓度之间的校准关系用于确定当纳米颗粒受到交变磁场作用时体积热生成率 (q'''(MNH)) 的分布。使用 SAS、MATLAB 和 EXCEL 处理扫描数据，以确定总发热率和各个 HU 范围内的纳米粒子分布体积。与对照组肿瘤相比，加热组肿瘤中的纳米颗粒不仅占据了注射部位附近，而且还占据了肿瘤外围。加热组中高q'''(MNH)范围(> 1.8 x10(6) W/m(3))的纳米粒子分布体积小10%，而在低q'''(MNH)范围0.6-1.8 x 10(6) W/m(3)时，加热组大95%。根据计算的各个HU范围的产热率，HU大于2000范围的百分比显着下降，从对照组的46%降至加热组的32%，而加热组HU范围500-1000和1000-1500的百分比则远高于对照组。加热 PC3 肿瘤 25 分钟导致纳米颗粒从肿瘤中的高浓度区域显着迁移到低浓度区域。基于局部加热前后纳米颗粒分布的体积产热率分布未来可用于指导磁性纳米颗粒热疗过程中纳米颗粒重新分布及其引起的PC3肿瘤温升的模拟，从而准确预测安全有效热疗所需的热剂量。
In magnetic nanoparticle hyperthermia, a required thermal dosage for tumor destruction greatly depends on nanoparticle distribution in tumors. The objective of this study is to conduct in vivo experiments to evaluate whether local heating using magnetic nanoparticle hyperthermia changes nanoparticle concentration distribution in prostatic cancer (PC3) tumors. In vivo animal experiments were performed on grafted PC3 tumors implanted in mice to investigate whether local heating via exposing the tumor to an alternating magnetic field (5 kA/m and 192 kHz) for 25 min resulted in nanoparticle spreading from the intratumoral injection site to tumor periphery. Nanoparticle redistribution due to local heating is evaluated via comparing microCT images of resected tumors after heating to those in the control group without heating. A previously determined calibration relationship between microCT Hounsfield unit (HU) values and local nanoparticle concentrations in the tumors was used to determine the distribution of volumetric heat generation rate (q'''(MNH)) when the nanoparticles were subject to the alternating magnetic field. SAS, MATLAB, and EXCEL were used to process the scanned data to determine the total heat generation rate and the nanoparticle distribution volumes in individual HU ranges. Compared to the tumors in the control group, nanoparticles in the tumors in the heating group occupied not only the vicinity of the injection site, but also tumor periphery. The nanoparticle distribution volume in the high q'''(MNH) range (> 1.8 x10(6) W/m(3)) is 10% smaller in the heating group, while in the low q'''(MNH) range of 0.6-1.8 x 10(6) W/m(3), it is 95% larger in the heating group. Based on the calculated heat generation rate in individual HU ranges, the percentage in the HU range larger than 2000 decreases significantly from 46% in the control group to 32% in the heating group, while the percentages in the HU ranges of 500-1000 and 1000-1500 in the heating group are much higher than that in the control group. Heating PC3 tumors for 25 min resulted in significant nanoparticle migration from high concentration regions to low concentration regions in the tumors. The volumetric heat generation rate distribution based on nanoparticle distribution before or after local heating can be used in the future to guide simulation of nanoparticle redistribution and its induced temperature rise in PC3 tumors during magnetic nanoparticle hyperthermia, therefore, accurately predicting required thermal dosage for safe and effective thermal therapy.