Quantitative comparison of delayed ferumoxytol T1 enhancement with immediate gadoteridol enhancement in high grade gliomas.

PURPOSE: Delayed ferumoxytol enhancement on T1 -weighted images appears visually similar to gadoteridol enhancement. The purpose of this study was to quantitatively compare ferumoxytol T1 enhancement to gadoteridol enhancement with an objective, semi-automated method. METHODS: 206 sets of post-gadoteridol and 24 h post-ferumoxytol T1 -weighted scans from 58 high grade glioma patients were analyzed (9 pre-chemoradiation, 111 < 90 days post-chemoradiation, 21 > 90 days post-chemoradiation, 65 post-bevacizumab scans). Enhancement volumes and signal intensities normalized to normal appearing tissue proximal to enhancement were calculated with a semi-automated method. Enhancement cube root volumes (D) and signal intensities (SI) were compared between the 2 contrast agents, and relative difference of D and SI were compared in different treatment groups with multivariate analysis. Within patient differences in D and SI before and after treatment with bevacizumab or steroid were assessed in 26 patients in each treatment group. RESULTS: When compared to gadoteridol, ferumoxytol D was 13.83% smaller and SI was 7.24% lower (P < 0.0001). The relative differences in D and SI between the 2 contrast agents were not significantly different between treatment groups (P > 0.05). Relative difference in D and SI did not change significantly in response to bevacizumab (P = 0.5234 and P = 0.2442, respectively) or to steroid (P = 0.3774, P = 0.0741) in the within patient comparison. CONCLUSION: The correlation between the 2 contrast agents' enhancement size and signal intensity and their similar behavior in response to therapy suggest that ferumoxytol can be used for revealing enhancement in high grade glioma patients. Magn Reson Med 80:224-230, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Dose escalation study of intravenous and intra-arterial N-acetylcysteine for the prevention of oto- and nephrotoxicity of cisplatin with a contrast-induced nephropathy model in patients with renal insufficiency.

BACKGROUND: Cisplatin neuro-, oto-, and nephrotoxicity are major problems in children with malignant tumors, including medulloblastoma, negatively impacting educational achievement, socioemotional development, and overall quality of life. The blood-labyrinth barrier is somewhat permeable to cisplatin, and sensory hair cells and cochlear supporting cells are highly sensitive to this toxic drug. Several chemoprotective agents such as N-acetylcysteine (NAC) were utilized experimentally to avoid these potentially serious and life-long side effects, although no clinical phase I trial was performed before. The purpose of this study was to establish the maximum tolerated dose (MTD) and pharmacokinetics of both intravenous (IV) and intra-arterial (IA) NAC in adults with chronic kidney disease to be used in further trials on oto- and nephroprotection in pediatric patients receiving platinum therapy. METHODS: Due to ethical considerations in pediatric tumor patients, we used a clinical population of adults with non-neoplastic disease. Subjects with stage three or worse renal failure who had any endovascular procedure were enrolled in a prospective, non-randomized, single center trial to determine the MTD for NAC. We initially aimed to evaluate three patients each at 150, 300, 600, 900, and 1200 mg/kg NAC. The MTD was defined as one dose level below the dose producing grade 3 or 4 toxicity. Serum NAC levels were assessed before, 5 and 15 min post NAC. Twenty-eight subjects (15 men; mean age 72.2 ± 6.8 years) received NAC IV (N = 13) or IA (N = 15). RESULTS: The first participant to experience grade 4 toxicity was at the 600 mg/kg IV dose, at which time the protocol was modified to add an additional dose level of 450 mg/kg NAC. Subsequently, no severe NAC-related toxicity arose and 450 mg/kg NAC was found to be the MTD in both IV and IA groups. Blood levels of NAC showed a linear dose response (p < 0.01). Five min after either IV or IA NAC MTD dose administration, serum NAC levels reached the 2-3 mM concentration which seemed to be nephroprotective in previous preclinical studies. CONCLUSIONS: In adults with kidney impairment, NAC can be safely given both IV and IA at a dose of 450 mg/kg. Additional studies are needed to confirm oto- and nephroprotective properties in the setting of cisplatin treatment. Clinical Trial Registration URL: https://eudract.ema.europa.eu . Unique identifier: 2011-000887-92.

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging.

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.