Appearance of primary lymphoid malignancies on lymphotropic nanoparticle-enhanced magnetic resonance imaging using ferumoxtran-10.

Patients with pathologically confirmed lymphoma/leukemia were retrospectively identified from a large single-institution phase III clinical trial with ferumoxtran-10. Five (2.3%) of 220 patients had lymphoid malignancies involving lymph nodes. A subset of patients (n=27) with biopsy-proven nodal metastases from genitourinary or breast cancer was selected as control group. Ferumoxtran-10 enhancement patterns and signal-to-noise ratios of lymph nodes involved by metastases and lymphoid malignancy were assessed. Like nodal metastases, nodes involved by lymphoid malignancies demonstrate persistent high T2*-signal intensity on lymphotropic nanoparticle-enhanced magnetic resonance imaging.

Detection of lymph nodes in pelvic malignancies with Computed Tomography and Magnetic Resonance Imaging.

Thirty patients with prostate or bladder cancer underwent CT and MRI for nodal staging. CT detected 189 nodes, and MRI detected 271 nodes. This difference was statistically significant in the external iliac (CT/MRI=73/87 nodes), obturator (CT/MRI=48/75 nodes), and internal iliac (CT/MRI=24/46 nodes) nodal chains. Based on size, the number of nodes detected by CT and MRI were as follows: 1-5 mm, CT/MRI=91/166; 6-10 mm, CT/MRI=91/98; >10 mm, CT/MRI=7/7 nodes. MRI detected significantly more lymph nodes in the size range of 1-5 mm.

Detection of nodal metastatic disease in patients with non-small cell lung cancer: comparison of positron emission tomography (PET), contrast-enhanced computed tomography (CT), and combined PET-CT.

Of 31 patients with lung cancer, 19 underwent PET-CT and 12 had CT followed by PET. Thoracic lymph nodes were sampled by mediastinoscopy or thoracotomy. Sensitivities, specificities, positive (PPV), and negative predictive values (NPV) were calculated based on histopathology. Ninety nodes (41 malignant) were identified. Sensitivity, specificity, PPV, and NPV were 94%, 73%, 66%, and 96% for PET-CT, respectively. In 12 patients who underwent PET and CT separately, these values were 90%, 31%, 64%, and 71% for PET and 81%, 50%, 69%, and 66% for CT, respectively.

Lymphotropic nanoparticle-enhanced magnetic resonance imaging (LNMRI) identifies occult lymph node metastases in prostate cancer patients prior to salvage radiation therapy.

Twenty-six patients with prostate cancer status post-radical prostatectomy who were candidates for salvage radiation therapy (SRT) underwent lymphotropic nanoparticle enhanced MRI (LNMRI) using superparamagnetic nanoparticle ferumoxtran-10. LNMRI was well tolerated, with only two adverse events, both Grade 2. Six (23%) of the 26 patients, previously believed to be node negative, tested lymph node positive by LNMRI. A total of nine positive lymph nodes were identified in these six patients, none of which were enlarged based on size criteria.

Overview of nanoparticle use in cancer imaging.

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.

The pharmacokinetics of the lymphotropic nanoparticle MRI contrast agent ferumoxtran-10.

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.

Current state and future applications of active targeting in malignancies using superparamagnetic iron oxide nanoparticles.

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.

Decreased bilateral cortical representation patterns in writer's cramp: a functional magnetic resonance imaging study at 3.0 T.

Functional magnetic resonance imaging was used to characterize patterns of cortical activation in response to sensory and motor tasks in patients with writer's cramp. 17 patients and 17 healthy subjects were examined during finger-tapping, index finger flexion, and electrical median nerve stimulation of both hands during electromyographic monitoring. SPM2 was used to evaluate Brodmann area (BA) 4, 1, 2, 3, 6, 40. Patients showed decreased activation in the left BA 4 with motor tasks of both hands and the left BA 1-3 with right finger-tapping. With left finger-tapping there was bilateral underactivation of single areas of the somatosensory cortex. Patients exhibited decreased activation in the bilateral BA 6 with left motor tasks and in the right BA 6 with right finger-tapping. Patients had decreased activation in bilateral BA 40 with finger-tapping of both hands. The findings suggest decreased baseline activity or an impaired activation in response to motor tasks in BA 1-4, 6, 40 in patients with writer's cramp for the dystonic and the clinically unaffected hand.

Uterine artery embolization in patients with symptomatic diffuse leiomyomatosis of the uterus.

Six patients with symptomatic diffuse uterine leiomyomatosis underwent technically successful uterine artery embolization. After a median follow-up of 16 months, five women presented with permanent alleviation of symptoms and a normalized quality of life according to the Uterine Fibroid Symptom and Quality of Life questionnaire. Magnetic resonance imaging showed impressive recovery of the myometrium, and the infarcted leiomyomas shrank and were partially expelled. No additional treatment was necessary. Failure of therapy occurred in one patient with atypical growth of fibroid tumor tissue shortly after embolization, which was suspicious for malignancy. Hysterectomy was performed and pathologic evaluation revealed benign leiomyomatosis.