Cancer Biomarkers - Volume 5, issue 2

Authors: Harisinghani, Mukesh G.

Article Type: Editorial

DOI: 10.3233/CBM-2009-0614

Citation: Cancer Biomarkers, vol. 5, no. 2, pp. 59-59, 2009

Authors: Islam, Tina | Harisinghani, Mukesh G.

Article Type: Research Article

Abstract: Current cross-sectional imaging modalities are inaccurate in characterizing nodal metastatic disease because of their use of size and/or morphology as differentiating factors. PET has overcome some of these limitations but it is constrained by its spacial resolution particularly for detecting small nodal metastases. These challenges have led to the development of lymphotropic contrast agents. Ferumoxtran-10 is one such MRI lymphotropic contrast agent that consists of ultrasmall superparamagnetic iron-oxide based nanoparticles targeted at the reticuloendothelial system. After intravenous administration ferumoxtran-10 is phagocytosed by macrophages which then accumulate within benign lymph nodes. Disturbances in lymph flow or in nodal architecture caused by …metastases lead to abnormal patterns of accumulation of the particles, which are detectable by MRI. On postcontrast T2- and T2*-weighted MRI benign lymph nodes show a drop in signal intensity and homogenous darkening whereas areas of malignant infiltration show lack of nanoparticle uptake and remain signal-intense. Summary ROC curve analysis for per-lymph-node data showed an overall sensitivity of 88% and overall specificity of 96% for ferumoxtran-10-enhanced MRI. Ferumoxtran-10-enhanced MRI offers higher diagnostic precision than unenhanced MRI and is sensitive and specific for the detection of lymph-node metastases, especially in malignant diseases of the abdomen and pelvis. Show more

Keywords: Ferumoxtran-10, ultrasmall superparamagnetic iron oxide particle (USPIO), lymph node, LNMRI, staging

DOI: 10.3233/CBM-2009-0578

Citation: Cancer Biomarkers, vol. 5, no. 2, pp. 61-67, 2009

Authors: Islam, Tina | Wolf, Gerald

Article Type: Research Article

Abstract: Ferumoxtran-10 is an ultrasmall superparamagnetic biodegradable iron oxide which serves as a MRI contrast agent in the differentiation of metastatic and non-metastatic lymph nodes in primary malignancies and imaging of phagocyte-associated disease processes. Ferumoxtran-10 is supplied as a lyophilized powder containing 210 mg of iron, 631 mg of dextran, and 27 mg of sodium citrate. The iron oxide core determines the magnetic properties of ferumoxtran-10, primarily its effects on the MR relaxation times, T1, T2, and T2*. Attachment of dextran prolongs the circulatory time of the nanoparticles. The intended human dose of ferumoxtran-10 is 2.6 mg Fe/kg. Reconstituted …and diluted with physiological saline it is administered intravenously by means of a slow drip infusion. After initial vascular distribution of the particles, they are slowly phagocytosed by the reticuloendothelial system cells of the spleen, lymph nodes, bone marrow, and liver. When ferumoxtran-10 is present in phagocytic cells the iron oxide causes local magnetic field inhomogeneities which lead to increases in proton relaxation rates, resulting in signal loss on mid-T1/T2 or heavily T2-weighted MR images. Stored in lysosomes the particles are ultimately degraded: the iron enters the normal body iron metabolism cycle and dextran is eliminated mainly via the kidney. Show more

Keywords: Ferumoxtran-10, ultrasmall superparamagnetic iron oxide particle, MRI contrast agent, macrophage phagocytosis

DOI: 10.3233/CBM-2009-0579

Citation: Cancer Biomarkers, vol. 5, no. 2, pp. 69-73, 2009

Authors: Eisner, Brian H. | Feldman, Adam S.

Article Type: Research Article

Abstract: Lymphotrophic nanoparticle enhanced magnetic resonance imaging is a promising new diagnostic modality for lymph node staging in genitourinary malignancies. The technique utilizes ultrasmall superparamagnetic iron oxide particles to provide detailed characterization of lymph nodes for detection of metastatic disease. Early results have are promising for bladder, penile, prostate, and testicular cancer. This review provides an overview of the current state of lymphotrophic enhanced magnetic resonance imaging in genitourinary cancers.

DOI: 10.3233/CBM-2009-0553

Citation: Cancer Biomarkers, vol. 5, no. 2, pp. 75-79, 2009

Authors: Narayanan, P. | Iyngkaran, T. | Sohaib, S.A. | Reznek, R.H. | Rockall, A.G.

Article Type: Research Article

Abstract: Lymph node status determines both prognosis and treatment choice in gynecological malignancies. Both CT and MRI are standard techniques used to detect lymph node involvement but these techniques have low sensitivity and specificity. Magnetic resonance lymphography (MRL) using iron oxide nanoparticles is a new technique for lymph node assessment which has shown much promise. This article discusses the applications of MRL in the setting of gynecological malignancy.

Keywords: Magnetic resonance lymphography (MRL), nanoparticles, gynecologic imaging

DOI: 10.3233/CBM-2009-0543

Citation: Cancer Biomarkers, vol. 5, no. 2, pp. 81-88, 2009

Authors: Koh, Dow-Mu | Brown, Gina | Collins, David J.

Article Type: Research Article

Abstract: Nanoparticles have been designed as novel contrast media for the evaluation of diseases. Ultrasmall iron oxide particles (USPIO) is a novel nanoparticle contrast medium, which is currently being evaluated as an MR lymphographic agent for the assessment of tumor spread to lymph nodes. Nodal disease is an independent poor prognostic indicator in patients with rectal cancer. Accurate pre-operative MR identification of patients with nodal disease and other adverse features can prompt the use of chemoradiation to downsize and downstage the disease, with the aim of reducing the long term risk of local and distant recurrence. In this article, we discuss …the challenges to accurate nodal staging of patients with rectal cancer, and demonstrate how USPIO may be applied to rectal cancer imaging to identify nodal involvement. Show more

DOI: 10.3233/CBM-2009-0544

Citation: Cancer Biomarkers, vol. 5, no. 2, pp. 89-98, 2009

Authors: Islam, Tina | Josephson, Lee

Article Type: Research Article

Abstract: Superparamagnetic iron oxide nanoparticles (SPIO) are novel MRI contrast agents. After cellular uptake, SPIO cause a negative T2 contrast in MRI. Passive targeting strategies rely on SPIO uptake in reticuloendothelial cells by receptor-mediated phagocytosis. Active targeting employs SPIO-conjugates with specific targeting ligands which selectively bind to biomarkers on target cells. Several receptor systems are overexpressed in cancerous diseases and have been investigated as targets for ligand-directed SPIO. Targeting receptors undergo repeated recycling to the cell surface and internalization and bind further SPIO, thereby amplifying the magnetic signal. Malignant cell degeneration may also lead to loss of specific receptor activity. SPIO-conjugates …directed at those receptors lead to a prominent reduction in signal intensity in healthy tissue but not the tumor. These strategies allow for molecular profiling of target cells and potentially enable the early detection of malignant diseases, more accurate staging, and treatment monitoring. With the advent of multimodality imaging techniques like targeted nanoparticle-enhanced MRI and near infrared optical fluorescence imaging, the combined advantages of different systems can be exploited. Show more

Keywords: Superparamagnetic iron oxide nanoparticles (SPIO), magnetic resonance imaging, oncologic imaging, receptor imaging, targeted probe, multimodality imaging

DOI: 10.3233/CBM-2009-0615

Citation: Cancer Biomarkers, vol. 5, no. 2, pp. 99-107, 2009