Magnetic resonance imaging diagnosis of metastatic lymph nodes in a rabbit model: efficacy of PJY10, a new ultrasmall superparamagnetic iron oxide agent, with monodisperse iron oxide core and multiple-interaction ligands

PLoS One. 2014 Sep 12;9(9):e107583. doi: 10.1371/journal.pone.0107583. eCollection 2014.

Abstract

Background: Accurate diagnosis of lymph node metastasis is crucial in treatment planning for cancer patients. Despite the use of various parameters, making correct diagnosis of a small metastatic or a hyperplastic benign node is still a challenge. In this study, we evaluated the feasibility of detecting lymph node metastasis using a new ultrasmall superparamagnetic iron oxide particle, PJY10, in a rabbit model.

Methods: To make metastatic and benign lymph nodes, either VX2 carcinoma or fecal material suspension was inoculated into thighs of 56 rabbits three weeks or three days before magnetic resonance (MR) imaging, respectively. T2*-weighted 3T MR imaging was performed before and 24 hours after PJY10 injection (5.2 [n = 15], 7.8 [n = 17], and 10.4 [n = 24] mg Fe/kg). MR images were correlated with pathologic results to calculate sensitivity and specificity. Quantitative analysis of the signal intensity (SI)--number of voxels[low] (the fraction of the number of voxels with the normalized SI on the postcontrast image lower than that on the precontrast image) and mean SI ratio--was also performed for each lymph node.

Results: Sensitivities were 100% at all three dosages, whereas specificity increased with increasing dosage (89% at 10.4 mg Fe/kg). The benign nodes had a significantly higher number of voxels[low] and a lower mean SI ratio than the metastatic nodes at the dosage of 10.4 mg Fe/kg (P<.001). Az values were 0.905 for the number of voxels[low] and 0.952 for the mean SI ratio. The number of voxels[low] (P = .019) and the mean SI ratio (P=.034) had significant correlations with the histopathologic area ratio of metastatic foci in the metastatic nodes at 10.4 mg Fe/kg.

Conclusions: PJY10 enabled clear demonstration of lymph node metastasis with high sensitivity and specificity at its optimal dosage of 10.4 mg Fe/kg.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media / chemistry*
  • Dextrans / chemistry
  • Disease Models, Animal
  • Ferric Compounds / chemistry*
  • Humans
  • Image Enhancement
  • Ligands
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / diagnosis
  • Lymphatic Metastasis / diagnostic imaging*
  • Lymphatic Metastasis / pathology
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles / chemistry
  • Nanoparticles / chemistry
  • Rabbits
  • Radiography

Substances

  • Contrast Media
  • Dextrans
  • Ferric Compounds
  • Ligands
  • Magnetite Nanoparticles
  • ferumoxtran-10
  • ferric oxide

Grants and funding

This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1120300), the Korea Healthcare technology R&D Projects, Ministry for Health, Welfare & Family Affairs (A112028), and the Research Center Program of IBS (Institute for Basic Science) in Korea. S.H.C. acknowledges financial support by Hanwha Chemicals Corp. The funder (Hanwha Chemical Corp.) provided support in the form of salaries for authors [BSJ, EBK, EGK, JP, WJM], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.