Abstract
BackgroundAccurate 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.MethodsTo 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.ResultsSensitivities 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.ConclusionsPJY10 enabled clear demonstration of lymph node metastasis with high sensitivity and specificity at its optimal dosage of 10.4 mg Fe/kg.
Highlights
When a malignancy is diagnosed in a patient, decision on which path the patient is to take thereafter for the better treatment outcome heavily relies on the presence of the spread of primary malignancy to regional or distant lymph nodes
Histopathology The numbers of benign and metastatic lymph nodes isolated from the rabbit models are summarized for each PJY10 dosage in Table 1. 10.4 mg Fe/kg of PJY10 was administered to 24 rabbits (12 tumor models and 12 inflammation models), whereas 7.8 mg Fe/kg of PJY10 was administered to 17 rabbits (11 tumor models and 6 inflammation models). 5.2 mg Fe/kg of PJY10 was administered to 15 rabbits (9 tumor models and 6 inflammation models)
The sensitivity was 100% (20 of 20, of 17, and of 18 in 5.2, 7.8, and 10.4 mg Fe/kg, respectively) in all three dosages, whereas the specificity increased with increasing dosage, with the dosage of 10.4 mg Fe/kg having the highest specificity of 89% (47 of 53)
Summary
When a malignancy is diagnosed in a patient, decision on which path the patient is to take thereafter for the better treatment outcome heavily relies on the presence of the spread of primary malignancy to regional or distant lymph nodes. Primary criterion for assessing the lymph node involvement has been the nodal size, with reported accuracies ranging from 63% to 75% for CT and 68% to 69% for MR imaging, respectively [1]. In an effort to improve the diagnostic accuracy, several studies have investigated various parameters – nodal morphology, border, signal intensity (SI) characteristics, enhancement kinetics, apparent diffusion coefficient, and 18F-fluorodeoxyglucose (18FFDG) and 18F-choline uptakes – for their added values in diagnosing metastatic lymph nodes [2,3,4,5,6,7,8,9,10]. Some promising results have been reported with the use of the parameters, the inherent limitation in diagnosing small metastatic or hyperplastic benign nodes has not been overcome, necessitating the development of a tissue-specific, highly sensitive and specific imaging technique to facilitate nodal characterization [1]. We evaluated the feasibility of detecting lymph node metastasis using a new ultrasmall superparamagnetic iron oxide particle, PJY10, in a rabbit model
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