Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging using ferumoxytol vs. gadoteridol: a pilot study.

PURPOSE: We evaluated dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging (DSC-MRI) using gadoteridol in comparison to the iron oxide nanoparticle blood pool agent, ferumoxytol, in patients with glioblastoma multiforme (GBM) who received standard radiochemotherapy (RCT). METHODS AND MATERIALS: Fourteen patients with GBM received standard RCT and underwent 19 MRI sessions that included DSC-MRI acquisitions with gadoteridol on Day 1 and ferumoxytol on Day 2. Relative cerebral blood volume (rCBV) values were calculated from DSC data obtained from each contrast agent. T1-weighted acquisition post-gadoteridol administration was used to identify enhancing regions. RESULTS: In seven MRI sessions of clinically presumptive active tumor, gadoteridol-DSC showed low rCBV in three and high rCBV in four, whereas ferumoxytol-DSC showed high rCBV in all seven sessions (p = 0.002). After RCT, seven MRI sessions showed increased gadoteridol contrast enhancement on T1-weighted scans coupled with low rCBV without significant differences between contrast agents (p = 0.9). Based on post-gadoteridol T1-weighted scans, DSC-MRI, and clinical presentation, four patterns of response to RCT were observed: regression, pseudoprogression, true progression, and mixed response. CONCLUSION: We conclude that DSC-MRI with a blood pool agent such as ferumoxytol may provide a better monitor of tumor rCBV than DSC-MRI with gadoteridol. Lesions demonstrating increased enhancement on T1-weighted MRI coupled with low ferumoxytol rCBV are likely exhibiting pseudoprogression, whereas high rCBV with ferumoxytol is a better marker than gadoteridol for determining active tumor. These interesting pilot observations suggest that ferumoxytol may differentiate tumor progression from pseudoprogression and warrant further investigation.

Magnetic resonance imaging of intracranial tumors: intra-patient comparison of gadoteridol and ferumoxytol.

This study aims to compare gadoteridol with ferumoxytol for contrast-enhanced and perfusion-weighted (PW) MRI of intracranial tumors. The final analysis included 26 patients, who underwent 3 consecutive days of 3T MRI. Day 1 consisted of anatomical pre- and postcontrast images, and PW MRI was acquired using gadoteridol (0.1 mmol/kg). On Day 2, the same MRI sequences were obtained with ferumoxytol (510 mg) and on Day 3, the anatomical images were repeated to detect delayed ferumoxytol-induced signal changes. The T1-weighted images were evaluated qualitatively and quantitatively for enhancement volume and signal intensity (SI) changes; PW data were used to estimate the relative cerebral blood volume (rCBV). All 26 lesions showed 24-hour T1-weighted ferumoxytol enhancement; 16 also had T2-weighted hypointensities. In 6 patients, ferumoxytol-induced signal changes were noted in areas with no gadoteridol enhancement. Significantly greater (P< .0001) SI changes were seen with gadoteridol, and qualitative analyses (lesion border delineation, internal morphology, contrast enhancement) also showed significant preferences (P= .0121; P = .0015; P < .0001, respectively) for this agent. There was no significant difference in lesion enhancement volumes between contrast materials. The ferumoxytol-rCBV values were significantly higher (P = .0016) compared with the gadoteridol-rCBV values. In conclusion, ferumoxytol provides important information about tumor biology that complements gadoteridol imaging. The rCBV measurements indicate areas of tumor undergoing rapid growth, whereas the 24-hour scans mark the presence of inflammatory cells. Both of these functions provide useful information about tumor response to treatment. We suggest that dynamic and anatomical imaging with ferumoxytol warrant further assessment in brain tumor therapy.

MR imaging of inflammation during myelin-specific T cell-mediated autoimmune attack in the EAE mouse spinal cord.

PURPOSE: The purpose of this study is to detect myelin-specific T cells, key pathological mediators in early multiple sclerosis, and the corresponding animal model, experimental autoimmune encephalomyelitis (EAE), in the mouse spinal cord. PROCEDURES: T cells were labeled with the iron-based, magnetic resonance (MR) contrast reagent, Feridex, and the transfection reagent, protamine sulfate, resulting in approximately 100% iron-labeling efficiency. Feridex-labeling did not alter the induction of EAE by T cells, and recipients were imaged by a 12-T MR instrument. RESULTS: Focal hypointense lesions were resolvable to gray or white matter of the lumbar spinal cord in T(2)-weighted images of the recipients of Feridex-labeled T cells. Lesions corresponded to histological evidence of inflammatory lesions and iron-labeled cells in eight-of-eight mice. In contrast, hypointense lesions were not observed eight-of-eight recipients of unlabeled T cells. CONCLUSIONS: These results demonstrate and provide methodologies for labeling, detecting, and extracting MRI-detectable foci of iron-labeled cells.

Solid-state NMR and 2,3-dicyano-5,7-dimethyl-6H-1,4-diazepine.

Crystalline 2,3-dicyano-5,7-dimethyl-6H-1,4-diazepine (A) was investigated by solid-state NMR spectroscopy, X-ray diffraction, and spectral simulations. The solid-state 13C NMR spectra of A display peculiar splittings for the methyl and cyano resonances. The crystal structure of A indicates that the methyl doublet is a consequence of two crystallographically inequivalent environments. The methyl motions associated with each site was examined via spin-lattice relaxation time (T1) measurements, and the carbon relaxation times (T(1)C) were used to calculate energy barriers to methyl rotation. The energy barriers to rotation were then used to correlate each methyl 13C shift with a particular crystallographic environment. The complex cyano splittings, however, are a result of both crystallographic inequivalence and residual 13C-14N dipolar coupling. The multiplet patterns of the isotropic shifts (centerbands) are dependent upon the magic-angle spinning (MAS) rate. Spectral simulations, using the perturbation method, of the centerbands and first-order sidebands were used to demonstrate, and elucidate, the observed MAS rate-dependent multiplet patterns of the cyano signals.

Solid-state NMR and the thermal polymerization of 2,4-hexadiyne-1,6-diol bis-(p-toluenesulfonate).

The solid-state thermal polymerization of crystalline 2,4-hexadiyne-1,6-diol bis-(p-toluenesulfonate) (PTS) was investigated by solid-state 13C NMR, the first application of this technique to such a process. The kinetics of the thermal process was examined at temperatures of 40.5, 51.0, and 59.5 degrees C, with a magic angle spinning (MAS) rate of 5 kHz. The first-order rate constants associated with the induction (k0) and autocatalytic (k max) periods were calculated by monitoring signal intensities (conversion) throughout the course of the thermal polymerization. While estimations of the activation energy (E(a) approximately 20 kcal/mol) from the NMR experiments are similar to values obtained by other analytical techniques, estimations of the autocatalytic effect (k max/k0 approximately 22) were significantly lower. Likely causes for the unusually small autocatalytic effect are discussed.

Solvent specified conformation in poly(alpha-L-glutamic acid) thin films.

The ability to control conformational properties of polypeptides in their films is of considerable interest for many possible applications of these materials. By rational choice of the solvent system for film fabrication, control over the conformation of the main chain, the intermolecular hydrogen bonding in the side chain is easily achieved in poly(alpha-L-glutamic acid) (PLGA) thin films. The spectral data from circular dichromism (CD), FT-IR, and solid state (13)C NMR spectroscopies suggest that the beta-sheet conformation is dominant in PLGA films cast from trifluoroacetic acid (TFA) solution, whereas the right-handed alpha-helix is dominant in those cast from pyridine or DMF solution. In comparison with films cast from TFA solutions, the films fabricated from pyridine or DMF solutions exhibit strong intermolecular hydrogen bondings between -COOH groups and have a more ordered arrangement of side chains. Moreover, the extent of alpha-helix conformation of the PLGA backbone in films cast from pyridine or DMF solution is several times higher than that observed in the PLGA powder precipitated from aqueous solution at pH 4. All spectroscopic studies indicate clearly that the solvents (used for casting these films) play a crucial role in directing the organization of PLGA in these thin films.

Diiminoisoindoline: tautomerism, conformations, and polymorphism.

Two polymorphs of the industrially important compound diiminoisoindoline occur in the amino tautomeric form as a conformational isomorph with a 1 : 1 mixture of the syn- and anti-isomers, and a conformational polymorph containing only the syn-isomer.