Abstract 358: The novel sentinel lymphnodes identification method using magnetic nanoparticle by MRI
Authors: Shuji Iida, Satoshi Itano, Sachiko Matsuda, Hirotoshi Hasegawa, Daisuke Kokuryo, Mamoru Hatakeyama, Hiroshi Handa, Ichio Aoki, Yuko Kitagawa
Journal: Cancer Research (2012)

Abstract [Introduction] Detection of sentinel lymph nodes (SN) has been used to predict regional lymph node (LN) metastasis in patients with various types of carcinoma. The technique used to detect SN has focused on using a vital blue dye, a radioactive tracer, or a combination of both. However there are several problems in the current method for SN identification, such as anaphylaxis shock, difficulties of detection, danger of radiation exposure, the limitation of use of radioisotopes, and short shelf life. The aim of this study was to develop new SN identification method using magnetic nanoparticles (MNPs) by MRI. [Methods] 5-week-old, Male Donryu rats were used for establishment of rat SN model and for optimization of MNPs size and amount. 4-week-old, male nude rats (F344/NJcl-rnu/rnu) were used for establishment of metastatic model. Three kinds of MNPs (4 nm (M4), 8 nm (M8), 20 nm (M20)) were synthesized. SN detectability was evaluated by T1-weighted gradient echo MR images after injection of synthesized MNPs or Resovist® in vivo. Signal change of LN induced by MNPs were evaluated T1-weighted MRI slice by two independent researchers. In addition, area (mm2) of susceptibility effect in LN was calculated using ROI tools of MRVision software. All MRI was examined for the receiver operating characteristic (ROC) curves by three individuals whether area of susceptibility was recognizable. ROC displaying sensitivity along with the false-positive rate (1αspecificity) for detecting MNPs by MRI, and the area under the curve with 95% confidence intervals was calculated. The amount of iron in the brachial lymph node (Br) and the axillary lymph node (Ax) was evaluated by inductively coupled plasma optical emission spectrometry (ICP-OES), and evaluated pathologically. MRI was performed weather Br and Ax were distinguishable. To evaluate toxicity of MNPs, exploratory single toxicity study was performed. Over all condition and weight status were observed. [Results] We established an original rat SN model and it revealed that Br is SN and Ax is a higher echelon nodes further downstream from SN. We also established metastatic rat model. M20 was sustained in Br selectively than M4, M8 and Resovist® and appropriate amount was 0.1mg. SN was distinguishable and detectable by MRI using M20 in normal and metastatic rat model. ROC curve analysis revealed that threshold of magnetite amount for MRI detection is 2.3μg/LN with 76.5% sensitivity and 25% specificity, and the area under receiver operating characteristic curve is 0.82 (95% CI, 0.64-1.0). Results of exploratory single toxicity study indicated that the fatal dose was equal to Resovist® and it was tolerable less than medium-low dose (1250 μmol/kg) injection. [Conclusion] We developed the novel SN identification method by MRI with our original 20nm MNPs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 358. doi:1538-7445.AM2012-358