Splenic imaging with ultrasmall superparamagnetic iron oxide ferumoxtran-10 (AMI-7227): preliminary observations

PURPOSE: Ferumoxtran-10 (ultrasmall superparamagnetic iron oxide; Combidex, AMI-7227) is a long-circulating MR contrast agent with reticuloendothelial uptake known to enhance tissue T1 and T2 relaxation rates. The purpose of this study was to assess the effect of ferumoxtran-10-enhanced MRI in evaluating focal splenic lesions. METHOD: Eighteen patients underwent MR evaluation of the spleen. Two of these patients with exophytic normal splenic tissue (splenules) and 13 of these patients with 24 focal splenic lesions (7 cysts, 2 hemangiomas, 7 metastases, 1 infarct, 7 lymphoma) were assessed by T1-weighted gradient echo and T2-weighted fast SE MRI following intravenous administration of ferumoxtran-10 (1.1 mg of Fe/kg). Qualitative analysis involving improved lesion detection and/or characterization, additional information from postcontrast images affecting staging, and patient management was performed. Quantitative measurements of lesion-to-spleen contrast-to-noise ratio were also performed. RESULTS: Additional information was provided by ferumoxtran-10-enhanced images in 15 of 18 patients. In 8 of 15 (53%) patients, improved lesion detection (i.e., number of lesions) was obtained on contrast-enhanced images. Improved lesion visualization (i.e., conspicuity) was noted in 11 of 15 (73%) of patients. In 10 of 15 (67%) patients, postcontrast imaging provided additional information leading to lesion characterization. Staging of disease and patient management were affected in 5 of 15 (33%) and 6 of 15 (40%) patients, respectively. CONCLUSION: Ferumoxtran-10 is a promising contrast agent for the evaluation of focal splenic lesions.     

An exploratory study of ferumoxtran-10 nanoparticles as a blood-brain barrier imaging agent targeting phagocytic cells in CNS inflammatory lesions

BACKGROUND AND PURPOSE: Iron oxide-based contrast agents have been investigated as more specific MR imaging agents for central nervous system (CNS) inflammation. Ferumoxtran-10 is a virus-size nanoparticle, taken up by reactive cells, that allows visualization of the phagocytic components of CNS lesions. Ferumoxtran-10 was compared with standard gadolinium-enhanced MR images in this exploratory trial to assess its potential in evaluation of CNS lesions with inflammatory aspects, including lymphoma, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and vascular lesions. METHODS: Twenty-three patients with different types of intracranial "inflammatory" lesions underwent standard brain MR with and without gadolinium, followed an average of 10 days later by a ferumoxtran-10 scan. Patients were imaged 24 hours after infusion of 2.6 mg/kg ferumoxtran-10. All MR images were evaluated subjectively by 4 investigators for a difference in enhancement patterns, which could be useful in differential diagnoses. RESULTS: In 5 cases, (one ADEM, 2 stroke, one cavernous venous vascular malformation, one primary central nervous lymphoma) the ferumoxtran-10 scan showed higher signal intensity, larger area of enhancement, or new enhancing areas compared with gadolinium. Most MS patients showed less enhancement with ferumoxtran-10 than with gadolinium. CONCLUSION: Ferumoxtran-10 showed different enhancement patterns in a variety of CNS lesions with inflammatory components in comparison to gadolinium. The impact of timing and therapy need further evaluation to better assess ferumoxtran-10 in addition to gadolinium as contrast agents for use in diagnosis and monitoring therapy in patients with CNS inflammatory lesions.     

MR imaging of mediastinal lymph nodes: evaluation using a superparamagnetic contrast agent

The purpose of this study was to determine whether intravenous injection of a magnetic resonance (MR) contrast agent, ultrasmall superparamagnetic iron oxide (ferumoxtran-10), can be useful in characterizing lymph nodes in patients with lung cancer. Twelve patients with known or suspected lung cancer were studied. Pre- and postcontrast injection of ferumoxtran-10 MR scans of the chest were obtained. Analysis of the signal intensities and bronchoscopic fine needle aspiration of a single node were performed in each patient. Six of 12 patients had a final diagnosis of lung cancer. T1-weighted images were best for localizing mediastinal lymph nodes. Signal intensity changes before and after contrast were best visualized on T2-weighted and gradient-echo images. All four patients with lung cancer who had nodes positive for malignancy at biopsy had no change in signal intensity of the nodes on T2 images. The signal intensity decreased in the remaining two patients, and the nodes were benign. Of the eight patients with benign disease, five had no change in signal intensity of the nodes. Therefore the sensitivity for tumor involvement of the nodes is 100%, but the specificity is only 37.5%. Ferumoxtran-10 is a contrast agent that can alter the signal intensity of lymph nodes. Lack of signal change may be due to malignant or inflammatory change. Studies in a larger population of lung cancer patients may help to characterize the utility of this agent further. J. Magn. Reson. Imaging 2000;12:899-904.     

Incidence of adverse events after I.V injection of MR contrast agents in a Chinese population. A comparison between gadopentetate and gadodiamide

PURPOSE: To study the incidence of adverse events after i.v. injection of MR contrast agents in a Chinese population. A comparison was made between an ionic contrast agent (dimeglumine gadopentetate, Magnevist) and a non-ionic contrast agent (gadodiamide, Omniscan). MATERIAL AND METHODS: During a 24-month period, 2,049 Chinese patients who randomly received an i.v. bolus injection of either Magnevist or Omniscan were investigated. All patients were questioned for the presence of any generalized or localized adverse reaction on the following day after the MR examination according to a standardized questionnaire. RESULTS: Three hundred and nine out of 2,049 patients (15%) reported an adverse event. There was a higher incidence of adverse events in patients receiving Magnevist as compared to those receiving Omniscan injection. All reported adverse events were clinically mild and required neither treatment nor hospitalization. CONCLUSION: There was a higher incidence of adverse reaction in patients receiving Magnevist than in those receiving Omniscan.     

Gadodiamide injection and gadopentetate dimeglumine. A double-blind study in MR imaging of the CNS.

A double-blind, randomized parallel phase III study in MR imaging of the central nervous system was conducted to compare the safety and diagnostic utility of gadodiamide injection and gadopentetate dimeglumine at a dose of 0.1 mmol/kg b.w. in 60 adult patients. Seven patients in the gadodiamide injection group experienced 10 adverse events, 5 of the events possibly related to the contrast agent. In the gadopentetate dimeglumine group 5 patients reported 3 contrast agent-related adverse events out of 8 events. All events were transient and required no treatment. Seven incidents of patient discomfort, and some minor changes in vital signs and laboratory parameters were of no clinical concern. Contrast enhancement was observed in 60% and 44% of the patients with structural abnormalities in the gadodiamide injection group and gadopentetate dimeglumine group, respectively. No difference in overall efficacy was observed. Gadodiamide injection was found to be a safe and effective contrast agent.     

Preclinical safety and pharmacokinetic profile of ferumoxtran-10, an ultrasmall superparamagnetic iron oxide magnetic resonance contrast agent

OBJECTIVES: This report presents an overview of preclinical data available on ferumoxtran-10, an ultrasmall superparamagnetic iron oxide nanoparticular contrast agent proposed for lymph node magnetic resonance imaging. MATERIALS AND METHODS: Pharmacokinetic, safety pharmacology, single- and repeat-dose toxicity, reproduction toxicity, and genotoxicity studies were performed with ferumoxtran-10 given intravenously (bolus injection) in mice, rats, rabbits, dogs, and monkeys. RESULTS: Ferumoxtran-10 was taken up by macrophages, mostly in liver, spleen, and lymph nodes, within 24 hours after bolus injection and underwent progressive metabolism. Toxicity was observed only at very high exposure levels and mainly was linked to a massive iron load after repeated injections. Ferumoxtran-10 was not mutagenic but was teratogenic in rats and rabbits. DISCUSSION: The preclinical pharmacokinetic and safety profile of ferumoxtran-10 appears to be satisfactory in view of its proposed use as a single-dose diagnostic agent in human for MR imaging of lymph nodes.     

Ferumoxtran-10-enhanced MR lymphangiography: does contrast-enhanced imaging alone suffice for accurate lymph node characterization?

OBJECTIVE: Ferumoxtran-10 is a lymphotropic MR contrast agent that is currently under investigation. It has been shown to be effective in staging lymph nodes of patients with various primary malignancies. The current technique with ferumoxtran-10 involves imaging before and 24 hr after contrast administration. The purpose of this study was to evaluate the accuracy of ferumoxtran-10-enhanced images alone in characterizing lymph nodes for oncologic staging 24 hr after contrast enhancement. MATERIALS AND METHODS: Seventy-seven patients (58 men, 19 women) with proven primary cancer (bladder [n = 20], breast [n = 10], endometrial [n = 1], renal [n = 3], penile [n = 4], prostate [n = 31], rectal [n = 1], testicular [n = 5], and ureteral [n = 2]) who were scheduled for surgical lymph node dissection were enrolled in the study. In these patients, 169 lymph nodes (mean size, 11.2 mm) were evaluated on T2*-weighted gradient-refocused echo MRI at l.5 T both before and 24-36 hr after the IV administration of ferumoxtran-10 (2.6 mg Fe/kg). Two blinded reviewers with differing levels of interpreting experience separately performed qualitative image evaluation. A 6-point scale was used to characterize lymph nodes on contrast-enhanced images alone and on combined unenhanced and contrast-enhanced images. Receiver operating characteristic (ROC) analysis was performed separately for both reviewers. RESULTS: Of the 169 lymph nodes evaluated, 55 were benign and 114 malignant by histopathologic analysis. The results of the ROC analysis comparing contrast-enhanced images ([A(z) = area under ROC curve] reviewer 1, A(z) = 0.92; reviewer 2, A(z) = 0.94) alone with combined unenhanced and contrast-enhanced images (reviewer 1, A(z) = 0.94; reviewer 2, A(z) = 0.93) showed a statistically significant difference (p = 0.01) for reviewer 1 but no difference for reviewer 2 (p = 0.88). Reviewer 2 was more experienced in interpreting ferumoxtran-10-enhanced images than reviewer 1. CONCLUSION: On ferumoxtran-10-enhanced MR lymphangiography, contrast-enhanced images alone may suffice for lymph node characterization. However, a certain level of interpretation experience may be required before contrast-enhanced images can be used alone.     

BOLD and CBV-weighted functional magnetic resonance imaging of the rat somatosensory system.

A multislice spin echo EPI sequence was used to obtain functional MR images of the entire rat brain with blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) contrast at 11.7 T. Maps of activation incidence were created by warping each image to the Paxinos rat brain atlas and marking the extent of the activated area. Incidence maps for BOLD and CBV were similar, but activation in draining veins was more prominent in the BOLD images than in the CBV images. Cerebellar activation was observed along the surface in BOLD images, but in deeper regions in the CBV images. Both effects may be explained by increased signal dropout and distortion in the EPI images after administration of the ferumoxtran-10 contrast agent for CBV fMRI. CBV-weighted incidence maps were also created for 10, 20, and 30 mg Fe/kg doses of ferumoxtran-10. The magnitude of the average percentage change during stimulation increased from 4.9% with the 10 mg Fe/kg dose to 8.7% with the 30-mg Fe/kg dose. Incidence of activation followed a similar trend.     

USPIO-enhanced magnetic resonance imaging for nodal staging in patients with head and neck cancer

PURPOSE: To determine the accuracy of ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) for nodal staging in patients with head and neck cancer. MATERIALS AND METHODS: Twenty patients with carcinomas of the upper aerodigestive tract were prospectively enrolled. MRI was performed before and 24-36 hours after intravenous infusion of an USPIO agent, ferumoxtran-10 (Sinerem; Guerbet, France; and Combidex; Advanced Magnetics) at a dose of 2.6 mg Fe/kg using T2-weighted spin-echo and gradient-echo sequences. Surgery was performed the same day or the day after the ferumoxtran-10-enhanced MR examination. Based on MRI, selected nodes were surgically removed and directly correlated with pathology using hematoxylin-eosin (H&E) and Perls stainings. RESULTS: A total of 63 nodes were studied; 36 were nonmetastatic, 25 metastatic, and two inflammatory. Ferumoxtran-10-enhanced MRI allowed diagnosis of 24 metastatic and 30 nonmetastatic nodes, yielding a sensitivity of 96%, a specificity of 78.9%, a positive predictive value of 75%, and a negative predictive value of 96.8%, compared to 64%, 78.9%, 66.6%, and 76.9%, respectively, for nonenhanced MRI. Accuracy of ferumoxtran-10-enhanced MRI was 85.7%. The gradient-echo T2-weighted sequence was the most accurate to detect signal loss in nonmetastatic nodes. CONCLUSION: USPIO-enhanced MRI is useful for nodal staging of patients with head and neck cancers.     

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.     

Urinary bladder cancer: preoperative nodal staging with ferumoxtran-10-enhanced MR imaging

PURPOSE: To prospectively evaluate ferumoxtran-10-enhanced magnetic resonance (MR) imaging for nodal staging in patients with urinary bladder cancer. MATERIALS AND METHODS: Fifty-eight patients with proved bladder cancer were enrolled. Results of MR imaging performed before and after injection of ferumoxtran-10 were compared with histopathologic results in surgically removed lymph nodes. High-spatial-resolution three-dimensional T1-weighted magnetization-prepared rapid acquisition gradient-echo (voxel size, 1.4 x 1.4 x 1.4 mm) and T2*-weighted gradient-echo (voxel size, 0.8 x 0.8 x 3.0 mm) sequences were performed before and 24 hours after injection of ferumoxtran-10 (2.6 mg iron per kilogram of body weight). On precontrast images, lymph nodes were defined as malignant by using size and shape criteria (round node, >8 mm; oval, >10 mm axial diameter). On postcontrast images, nodes were considered benign if there was homogeneous decrease in signal intensity and malignant if decrease was absent or heterogeneous. Qualitative evaluation was performed on a node-to-node basis. Sensitivity, specificity, predictive values, and accuracy were evaluated with logistic regression analysis. RESULTS: In 58 patients, 172 nodes imaged with use of ferumoxtran-10 were matched and correlated with results of node dissection. Of these, 122 were benign and 50 were malignant. With nodal size and shape criteria, accuracy, sensitivity, specificity, and positive and negative predictive values on precontrast images were 92%, 76%, 99%, 97%, and 91%, respectively; corresponding values on postcontrast images were 95%, 96%, 95%, 89%, and 98%. In the depiction of pelvic metastases, sensitivity and negative predictive value improved significantly at postcontrast compared with those at precontrast imaging, from 76% to 96% (P < .001) and from 91% to 98% (P < .01), respectively. At postcontrast imaging, metastases (4-9 mm) were prospectively found in 10 of 12 normal-sized nodes (<10 mm); these metastases were not detected on precontrast images. Postcontrast images also showed lymph nodes that were missed at pelvic node dissection in two patients. CONCLUSION: Ferumoxtran-10-enhanced MR imaging significantly improves nodal staging in patients with bladder cancer by depicting metastases even in normal-sized lymph nodes.     

Ferric ammonium citrate as a positive bowel contrast agent for MR imaging of the upper abdomen. Safety and diagnostic efficacy.

PURPOSE: To evaluate the safety and diagnostic efficacy of two different doses of ferric ammonium citrate as a paramagnetic oral contrast agent for MR imaging of the upper abdomen. MATERIAL AND METHODS: Ninety-nine adult patients referred for MR imaging for a known or suspected upper abdominal pathology were included in this randomized multicenter double-blind clinical trial. Imaging was performed with spin-echo (T1- and T2-weighted) and gradient-echo (T1-weighted) techniques before and after administration of either 1200 mg or 2400 mg of ferric ammonium citrate dissolved in 600 ml of water. Safety analysis included monitoring of vital signs, assessment of adverse events, and laboratory testing. Efficacy with regard to organ distension, contrast distribution, bowel enhancement and delineation of adjacent structures was graded qualitatively. RESULTS: No serious adverse events were reported for either of the two concentrations. A total of 31 minor side effects were noted, of which significantly more occurred in the higher dose group (p<0.01). The diagnostic confidence in defining or excluding disease was graded as better after contrast administration for 48% of all images. Marked or moderate enhancement of the upper gastrointestinal tract was achieved at both doses in 69.5% of cases with no evident difference between the two doses. The higher dose tended to show better results in terms of the contrast assessment parameters. CONCLUSION: Ferric ammonium citrate is a safe and effective oral contrast agent for MR imaging of the upper abdomen at two different dose levels. The higher dose showed a tendency toward better imaging results while the lower dose caused significantly fewer side effects. Therefore the 1200 mg dose can be recommended in view of the risk-to-benefit ratio.     

Safety of ferucarbotran in MR imaging of the liver: A pre‐ and postexamination questionnaire‐based multicenter investigation

Purpose

To prospectively investigate, by means of a pre‐and postexamination questionnaire, the types and frequency of adverse reactions to ferucarbotran (Resovist), a superparamagnetic iron oxide (SPIO) contrast agent.

Materials and Methods

This study was approved by the ethics committee of each of the institutions involved, and all patients gave written informed consent. One questionnaire asking about baseline symptoms before the injection of ferucarbotran, and one about adverse events over a period of seven days after injection were given to 315 patients who underwent ferucarbotran‐enhanced magnetic resonance imaging (MRI) of the liver at several institutions. The data for baseline symptoms were used for reference to exclude false‐positive adverse reactions and were also compared with the adverse event data to determine with McNemar's chi‐squared test the incidence of each symptom.

Results

Before MR examination, 249 clinical symptoms were reported by 102 of 315 patients (32.4%). After the injection of ferucarbotran, 169 adverse events were observed in 78 patients (24.8%). Eventually, 70 adverse events occurring in 45 patients (14.3%) were judged to be adverse reactions to ferucarbotran, defined as possibly or definitely ferucarbotran‐related events. All reactions were of mild intensity.

Conclusion

Ferucarbotran can be considered safe for clinical use in liver MRI. J. Magn. Reson. Imaging 2009;29:106–111. © 2008 Wiley‐Liss, Inc.     

Prostate cancer evaluated with ferumoxtran-10-enhanced T2*-weighted MR Imaging at 1.5 and 3.0 T: early experience

PURPOSE: To prospectively evaluate the feasibility of ferumoxtran-10-enhanced magnetic resonance (MR) imaging at high magnetic field strength (3.0 T) and to compare image quality between 1.5- and 3.0-T MR imaging in terms of lymph node detection in patients with prostate cancer. MATERIALS AND METHODS: This study was institutional review board approved, and all patients gave written informed consent. Forty-eight consecutive patients aged 51-79 years (mean, 65.5 years) with prostate cancer were enrolled. T2*-weighted 1.5- and 3.0-T MR images of the pelvis were acquired in a sagittal plane parallel to the psoas muscle 24 hours after ferumoxtran-10 administration. A pelvic and body phased-array coil was used and yielded an in-plane resolution of 0.56 x 0.56 x 3.00 mm at 1.5 T and 0.50 x 0.50 x 2.50 mm at 3.0 T. All images were evaluated by three readers for total image quality, lymph node border delineation, muscle-fat contrast, and vessel-fat contrast. Statistical significance was calculated by using the Mann-Whitney U test. Subsequently, the general linear mixed model was used to estimate the contributions of three factors-patient, reader, and technique-to the variability of the imaging results. RESULTS: Significantly (P < .05) better muscle-fat contrast, vessel-fat contrast, lymph node border delineation, and total image quality were observed at 3.0-T MR imaging. The general linear mixed model revealed that the variability of all results could be attributed to the use of 3.0-T imaging. CONCLUSION: Ferumoxtran-10-enhanced MR imaging can be performed at high magnetic field strengths and result in improved image quality, which may lead to improved detection of small positive lymph nodes.     

Ferumoxtran-10, a superparamagnetic iron oxide as a magnetic resonance enhancement agent for imaging lymph nodes: a phase 2 dose study

BACKGROUND AND PURPOSE: Dextran-coated ultrasmall superparamagnetic iron oxide ferumoxtran-10 (Combidex) is used in reticuloendothelial MR imaging. Our purpose was to determine the optimal dose and imaging time for lymph node evaluation. MATERIALS: Twenty-four healthy volunteers underwent neck MR imaging before and 6, 12, 24, and 36 hours after receiving 1.1, 1.7, 2.6, or 3.4 mg Fe/kg ferumoxtran-10. Vital signs, serum and urine levels, and adverse events were monitored. Qualitative nodal architecture, size, and signal-intensity changes were assessed on T1-, T2-, and T2*-weighted (fast field-echo 25 degrees or 80 degrees flip angle [FFE-25 or FFE-80]) images. Region-of-interest intensities were measured quantitatively. RESULTS: Consistently strong enhancement in normal nodes was found with 24- and 36-hour T2- and T2*-weighted imaging after 2.6 and 3.4 mg Fe/kg doses. No serious adverse events occurred. With 2.6 mg Fe/kg, unblinded (vs blinded) specificities at 24 and 36 hours, respectively, were 100% and 100% (vs 88% and 88%) with T2-weighted, 96% and 96% (vs 73% and 85%) with FFE-25, and 100% and 92% (vs 85% and 88%) with FFE-80 sequences. With 3.4 mg Fe/kg, unblinded (vs blinded) specificities at 24 and 36 hours, respectively, were 89% and 79% (vs 75% and 75%) with T2-weighted, 84% and 79% (vs 95% and 100%) with FFE-25, and 95% and 79% (vs 95% and 80%) with FFE-80 sequences. CONCLUSION: Ferumoxtran-10 nodal imaging appears to be effective and safe. Signal intensity and specificity for normal nodes were best 24 or 36 hours after 2.6 and 3.4 mg Fe/kg doses. Nodal conspicuity was best with T2- and T2*-weighted sequences.     

Ultrasmall superparamagnetic iron-oxide-enhanced MR imaging of normal bone marrow in rodents: original research original research

RATIONALE AND OBJECTIVES: The objective is to compare three different ultrasmall superparamagnetic iron oxides (USPIOs) for magnetic resonance (MR) imaging of normal bone marrow in rodents. MATERIALS AND METHODS: Femoral bone marrow in 18 Sprague-Dawley rats was examined by using MR imaging before and up to 2 and 24 hours postinjection (PI) of 200 mumol of Fe/kg of SHU555C (n = 6), ferumoxtran-10 (n = 6), or ferumoxytol (n = 6), using T1-weighted (50 ms/1.7 ms/60 degrees = repetition time [TR]/echo time [TE]/flip angle) and T2*-weighted (100 ms/15 ms/38 degrees = TR/TE/flip angle) three-dimensional spoiled gradient recalled echo sequences. USPIO-induced bone marrow was evaluated qualitatively and quantified as signal-to-noise ratio (SNR) and change in signal intensity (DeltaSI) values. A mixed-effect model was fitted to the SNR and DeltaSI values, and differences among USPIOs were tested for significance by using F tests. RESULTS: At 2 hours PI, all three USPIOs showed marked positive signal enhancement on T1-weighted images and a corresponding marked signal loss on T2*-weighted images. At 24 hours PI, the T1 effect of all three USPIOs disappeared, whereas T2*-weighted images showed persistent signal loss on SHU555C and ferumoxytol-enhanced MR images, but not ferumoxtran-10-enhanced MR images. Corresponding SNR and DeltaSI values on T2*-weighted MR images at 24 hours PI were significantly different from baseline for SHU555C and ferumoxytol, but not ferumoxtran-10. CONCLUSION: All three USPIO contrast agents, ferumoxtran-10, ferumoxytol, and SHU555C, can be applied for MR imaging of bone marrow. Ferumoxtran-10 apparently reveals a different kinetic behavior in bone marrow than ferumoxytol and SHU555C.     

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.     

A summary of safety of gadofosveset (MS-325) at 0.03 mmol/kg body weight dose: Phase II and Phase III clinical trials data

OBJECTIVE: We sought to summarize the Phase II and Phase III clinical trials safety data for gadofosveset (Vasovist, MS-325), a new magnetic resonance angiography contrast agent. MATERIALS AND METHODS: Subjects with known or suspected vascular disease were administered 0.03 mmol/kg gadofosveset (767 subjects) or placebo (49 subjects) in phase II and phase III studies. Overall safety data were pooled from 8 studies and included adverse event monitoring, clinical laboratory assays, vital signs, oxygen saturation, physical examination, and electrocardiography. The safety was monitored for 72 to 96 hours postinjection (PI), and safety comparison with x-ray angiography using iodinated contrast media also was performed in 318 subjects. In the phase II trial, 5 doses of gadofosveset and placebo were evaluated. In this study, 38 patients were administered placebo and 39 patients received 0.03 mmol/kg gadofosveset. RESULTS: In pooled data, treatment related adverse events were reported by 176 (22.9%) patients receiving gadofosveset and by 16 (32.7%) patients receiving placebo. In phase II trial, treatment-related adverse events were reported by 13 of the 39 (33.3%) patients receiving gadofosveset and 9 of the 38 (23.7%) patients receiving placebo. No severe or serious adverse events were reported in either gadofosveset or placebo groups in this phase II trial. Pooled data revealed no clinically significant trends in adverse events, laboratory assays, vital signs, or oxygen saturation. A QTc prolongation of 2.8 milliseconds was observed at 45 minutes after MS-325 injection; however, this trend was similar to that of the placebo group at the same time point (3.2 milliseconds). CONCLUSION: Gadofosveset has exhibited a good safety profile and can be safely administered as an intravenous bolus injection. The overall rate and experience of adverse events was similar to that of placebo. The safety profile of gadofosveset is comparable with that of other gadolinium contrast agents as reported in the literature.     

Differential uptake of ferumoxtran-10 and ferumoxytol, ultrasmall superparamagnetic iron oxide contrast agents in rabbit: critical determinants of atherosclerotic plaque labeling

PURPOSE: To compare atherosclerotic plaque uptake of a first (ferumoxtran-10) and second generation (ferumoxytol) ultrasmall superparamagnetic iron oxide (USPIO) contrast agent with different pharmacokinetic/pharmacodynamic properties. MATERIALS AND METHODS: New Zealand White rabbits maintained on a high cholesterol/fat diet were subjected to balloon injury to the abdominal aorta. Ferumoxtran-10 or ferumoxytol (500 micromol/kg) was administered at 2, 4, and 8 weeks following injury. In vivo magnetic resonance imaging (MRI) was performed immediately prior to, immediately after, and 6 days post-contrast administration. Ex vivo MRI, histologic, and inductively coupled plasma-mass spectrometry (ICP-MS) iron analyses were performed on the excised vessels. RESULTS: The blood pool clearance of ferumoxytol (t(1/2) < or = 6 hours) was more rapid than that of ferumoxtran-10 (t(1/2) < or = 48 hours). Decreased in vivo MRI signal intensity in the abdominal aorta was observed at 2, 4, and 8 weeks following injury with ferumoxtran-10, but not with ferumoxytol. Consistent with these observations, ex vivo MRI signal intensity was decreased in the ferumoxtran-10 vessels, and to a lesser degree in the ferumoxytol vs. control vessels (- contrast agent). In contrast, in vitro macrophage phagocytosis of USPIO was four to six fold greater with ferumoxytol than with ferumoxtran-10. Additionally, the absolute iron content correlated with ex vivo MRI signal intensity in all vessels (r = -0.86, P < 0.0001). CONCLUSIONS: These data suggest that the exposure period of atherosclerotic plaque to USPIO rather than the kinetics of the USPIO uptake by plaque alone is a critical criterion for experimental design of in vivo studies.