Chieh Jen-Jie, Huang Kai-Wen, Lee Yi-Yan, Wei Wen-Chun
Institute of Electro-Optical Science and Technology, National Taiwan Normal University, Taipei, 116, Taiwan.
Department of Surgery and Hepatitis Research Center, National Taiwan University Hospital, Taipei, 100, Taiwan.
J Nanobiotechnology. 2015 Feb 12;13:11. doi: 10.1186/s12951-015-0069-5.
For intraoperative imaging in operating theaters or preoperative imaging in clinics, compact and economic integration rather than large and expensive equipment is required to coregister structural and functional imaging. However, current technologies, such as those integrating optical and gamma cameras or infrared and fluorescence imaging, involve certain drawbacks, including the radioactive biorisks of nuclear medicine indicators and the inconvenience of conducting measurements in dark environments.
To specifically and magnetically label liver tumors, an anti-alpha-fetoprotein (AFP) reagent was synthesized from biosafe iron oxide magnetic nanoparticles (MNPs) coated with anti-AFP antibody and solved in a phosphate buffered saline solution. In addition, a novel dual-imaging model system integrating an optical camera and magnetic scanning superconducting-quantum-interference device (SQUID) biosusceptometry (SSB) was proposed. The simultaneous coregistration of low-field magnetic images of MNP distributions and optical images of anatomical regions enabled the tumor distribution to be determined easily and in real time. To simulate targeted MNPs within animals, fewer reagents than the injected dose were contained in a microtube as a sample for the phantom test. The phantom test was conducted to examine the system characteristics and the analysis method of dual images. Furthermore, the animal tests were classified into two types, with liver tumors implanted either on the backs or livers of rats. The tumors on the backs were to visually confirm the imaging results of the phantom test, and the tumors on the livers were to simulate real cases in hepatocellular carcinoma people.
A phantom test was conducted using the proposed analysis method; favorable contour agreement was shown between the MNP distribution in optical and magnetic images. Consequently, the positioning and discrimination of liver tumors implanted on the backs and livers of rats were verified by conducting in vivo and ex vivo tests. The results of tissue staining verified the feasibility of using this method to determine the distribution of liver tumors.
The results of this study indicate the clinical potential of using anti-AFP-mediated MNPs and the dual-imaging model SSB for discriminating and locating tumors.
对于手术室中的术中成像或诊所中的术前成像,需要紧凑且经济的集成设备,而非大型且昂贵的设备来对结构成像和功能成像进行配准。然而,当前的技术,如集成光学相机和伽马相机或红外与荧光成像的技术,存在某些缺点,包括核医学指标的放射性生物风险以及在黑暗环境中进行测量的不便。
为了特异性地磁性标记肝肿瘤,由包被有抗甲胎蛋白(AFP)抗体的生物安全氧化铁磁性纳米颗粒(MNP)合成了一种抗AFP试剂,并将其溶解在磷酸盐缓冲盐溶液中。此外,提出了一种集成光学相机和磁扫描超导量子干涉装置(SQUID)生物磁测量法(SSB)的新型双成像模型系统。MNP分布的低场磁图像与解剖区域的光学图像的同时配准使得能够轻松实时地确定肿瘤分布。为了在动物体内模拟靶向MNP,在微管中装入比注射剂量少的试剂作为体模测试的样本。进行体模测试以检查系统特性和双图像分析方法。此外,动物测试分为两种类型,在大鼠的背部或肝脏植入肝肿瘤。背部的肿瘤用于直观确认体模测试的成像结果,肝脏上的肿瘤用于模拟肝癌患者的实际病例。
使用所提出的分析方法进行了体模测试;光学图像和磁图像中的MNP分布之间显示出良好的轮廓一致性。因此,通过体内和体外测试验证了植入大鼠背部和肝脏的肝肿瘤的定位和辨别。组织染色结果证实了使用该方法确定肝肿瘤分布的可行性。
本研究结果表明使用抗AFP介导的MNP和双成像模型SSB鉴别和定位肿瘤的临床潜力。