Hoopes Pj, Strawbridge Rr, Gibson Uj, Zeng Q, Pierce Ze, Savellano M, Tate Ja, Ogden Ja, Baker I, Ivkov R, Foreman Ar
Dartmouth College Hanover, NH.
Triton Biosystems Chelmsford, MA.
Proc SPIE Int Soc Opt Eng. 2007 Feb 13;6440:64400K. doi: 10.1117/12.706302.
The potential synergism and benefit of combined hyperthermia and radiation for cancer treatment is well established, but has yet to be optimized clinically. Specifically, the delivery of heat via external arrays /applicators or interstitial antennas has not demonstrated the spatial precision or specificity necessary to achieve appropriate a highly positive therapeutic ratio. Recently, antibody directed and possibly even non-antibody directed iron oxide nanoparticle hyperthermia has shown significant promise as a tumor treatment modality. Our studies are designed to determine the effects (safety and efficacy) of iron oxide nanoparticle hyperthermia and external beam radiation in a murine breast cancer model.
MTG-B murine breast cancer cells (1 × 10) were implanted subcutaneous in 7 week-old female C3H/HeJ mice and grown to a treatment size of 150 mm +/- 50 mm. Tumors were then injected locally with iron oxide nanoparticles and heated via an alternating magnetic field (AMF) generator operated at approximately 160 kHz and 400 - 550 Oe. Tumor growth was monitored daily using standard 3-D caliper measurement technique and formula. specific Mouse tumors were heated using a cooled, 36 mm diameter square copper tube induction coil which provided optimal heating in a 1 cm wide region in the center of the coil. Double dextran coated 80 nm iron oxide nanoparticles (Triton Biosystems) were used in all studies. Intra-tumor, peri-tumor and rectal (core body) temperatures were continually measured throughout the treatment period.
Preliminary in vivo nanoparticle-AMF hyperthermia (167 KHz and 400 or 550 Oe) studies demonstrated dose responsive cytotoxicity which enhanced the effects of external beam radiation. AMF associated eddy currents resulted in nonspecific temperature increases in exposed tissues which did not contain nanoparticles, however these effects were minor and not injurious to the mice. These studies also suggest that iron oxide nanoparticle hyperthermia is more effective than nonnanoparticle tumor heating techniques when similar thermal doses are applied. Initial electron and light microscopy studies of iron oxide nanoparticle and AMF exposed tumor cells show a rapid uptake of particles and acute cytotoxicity following AMF exposure.
热疗与放疗联合用于癌症治疗的潜在协同作用和益处已得到充分证实，但在临床上尚未得到优化。具体而言，通过外部阵列/施药器或间质天线传递热量尚未显示出实现适当的高治疗比所需的空间精度或特异性。最近，抗体导向甚至可能是非抗体导向的氧化铁纳米颗粒热疗作为一种肿瘤治疗方式已显示出巨大的前景。我们的研究旨在确定氧化铁纳米颗粒热疗和外照射在小鼠乳腺癌模型中的效果（安全性和有效性）。
将MTG-B小鼠乳腺癌细胞（1×10）皮下植入7周龄雌性C3H/HeJ小鼠体内，生长至治疗大小为150 mm±50 mm。然后在肿瘤局部注射氧化铁纳米颗粒，并通过以约160 kHz和400 - 550 Oe运行的交变磁场（AMF）发生器进行加热。使用标准的三维卡尺测量技术和公式每天监测肿瘤生长情况。使用冷却的、直径36 mm的方形铜管感应线圈对特定的小鼠肿瘤进行加热，该线圈在其中心1 cm宽的区域提供最佳加热效果。所有研究均使用双重葡聚糖包被的80 nm氧化铁纳米颗粒（Triton Biosystems）。在整个治疗期间持续测量肿瘤内、肿瘤周围和直肠（核心体温）温度。
初步的体内纳米颗粒-AMF热疗（167 KHz和400或550 Oe）研究表明存在剂量反应性细胞毒性，增强了外照射的效果。AMF相关的涡电流导致不含纳米颗粒的暴露组织出现非特异性温度升高，然而这些影响较小，对小鼠无害。这些研究还表明，当施加相似的热剂量时，氧化铁纳米颗粒热疗比非纳米颗粒肿瘤加热技术更有效。对氧化铁纳米颗粒和AMF暴露的肿瘤细胞进行的初步电子显微镜和光学显微镜研究显示，颗粒摄取迅速，AMF暴露后具有急性细胞毒性。
