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C Corot

Publications and source records attributed to C Corot.

At least 19 recordsLinked to original sources
PubMed2005

Distribution of gadomelitol in a human breast tumor model in mice.

The study evaluates the tumor distribution of the rapid clearance blood pool agent (RCBPA) gadomelitol, in a breast tumor model. Different techniques were used : (1) tissue gadolinium concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES), (2) whole body quantitative autoradiography using radiolabeled [153Gd] gadomelitol and (3) dynamic contrast-enhanced MRI with compartmental analysis. An accumulation of gadomelitol in tumors compared to muscle was observed 30 min and 3 h post injection (p.i.). Thirty minutes p.i., the gadomelitol tumor distribution evaluated by autoradiography showed a marked difference between the rim and the center, whereas both areas showed comparable concentrations after 3 h. Using dynamic contrast-enhanced MRI, three phases could be observed during the 1 hour observation period: (1) rapid tumor uptake within the first few minutes post-injection (2) a progressive increase in tumor signal enhancement over 10 min and (3) a steady-state phase. Average +/- SD (n=5) transendothelial permeability K(PS) and the fractional blood volume fBV were 12.2+/-1.6 microl/min(-1)/g and 5.4+/-0.2% respectively. Due to its slow extravasation and high tumor residence time, gadomelitol may potentially be useful to improve characterization between benign versus malignant tumors using dynamic MRI.

Animals↗
PubMed2001

Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits.

BACKGROUND: Based on the observation that ultrasmall superparamagnetic particles of iron oxides (USPIOs) are phagocytosed by cells of the mononuclear phagocytic system, the purpose of this study was to evaluate their use as a marker of atherosclerosis-associated inflammatory changes in the vessel wall before luminal narrowing is present. METHODS AND RESULTS: Experiments were conducted on 6 heritable hyperlipidemic and 3 New Zealand White rabbits. 3D MR angiography (MRA) of the thoracic aorta was performed on all rabbits by use of a conventional paramagnetic contrast agent that failed to reveal any abnormalities. One week later, all rabbits except 1 of the hyperlipidemic animals were injected with a USPIO contrast agent (Sinerem, Guerbet) at a dose of 1 mmol Fe/kg. 3D MRA data sets collected over the subsequent 5 days showed increasing signal in the aortic lumen. Whereas the aortic wall of the control rabbits remained smooth and bright, marked susceptibility effects became evident on day 4 within the aortic walls of hyperlipidemic rabbits. Ex vivo imaging of aortic specimens confirmed the in vivo results. Histopathology documented marked Fe uptake in macrophages embedded in atherosclerotic plaque of the hyperlipidemic rabbits. Electron microscopy showed multiple cytoplasmic Fe particles in macrophages. No such changes were seen in control rabbits or in the hyperlipidemic rabbit that had not received Sinerem. CONCLUSIONS: USPIOs are phagocytosed by macrophages in atherosclerotic plaques of the aortic wall of hyperlipidemic rabbits in a quantity sufficient to cause susceptibility effects detectable by MRI.

Animals↗
PubMed2001

A new gadolinium-based contrast agent for magnetic resonance imaging of brain tumors: kinetic study on a C6 rat glioma model.

T1-weighted magnetic resonance imaging (MRI) was used to evaluate the potential interest of a new Gd-based contrast agent, termed P760, to characterize brain tumor heterogeneity and vascularization and to delineate regions containing permeable vessels. The C6 rat glioma model was used as a model of high-grade glioblastoma. The signal enhancement was measured as a function of time in the vascular compartment and in different regions of interest (ROIs) within the tumor after the injection of 0.02 mmol x kg(-1) of P760. The results were compared to those obtained after the injection of 0.1 mmol x kg(-1) of Gd-DOTA. We showed that P760, in spite of a Gd concentration five times smaller, produces an enhancement in the blood pool similar to that produced by Gd-DOTA. It was shown that P760 makes possible an excellent delineation of regions containing vessels with a damaged blood-brain barrier (BBB). Images acquired 5-10 minutes after P760 injection showed the location of permeable vessels more accurately than Gd-DOTA-enhanced images. The enhancement produced in the tumor by P760 was, however, less than that produced by Gd-DOTA. The extravasation and/or diffusion rate of P760 in the interstitial medium were found to be strongly reduced, compared to those found with Gd-DOTA. This study suggests that the new contrast agent has promising capabilities in clinical imaging of brain tumors.

Animals↗
PubMed2001

Assessment of a rapid clearance blood pool MR contrast medium (P792) for assays of microvascular characteristics in experimental breast tumors with correlations to histopathology.

The diagnostic potential of a new rapid clearance blood pool contrast medium (P792; MW = 6.47 kDa) for the MR assessment of microvessel characteristics was assessed in 42 chemically-induced breast tumors, with comparisons to albumin-(Gd-DTPA). Microvessel characteristics, including the transendothelial permeability (K(PS)) and the fractional blood volume (fPV), were estimated by using dynamic MR data fit to a bidirectional two-compartment model. The MR-derived estimates for K(PS) and fPV using each contrast agent were compared, and assays using each contrast agent were correlated to the histologic tumor grade (SBR score) and the microvascular density (MVD) counts. Using P792-enhanced data, neither K(PS) nor fPV showed a statistically significant correlation with the tumor grade or the MVD (P >.05). Conversely, using albumin-(GdDTPA)(30), K(PS) values correlated significantly with the histologic tumor grade (r =.55; P <.0005) and the MVD (r =.34, P <.05), whereas no correlation was established for fPV. In conclusion, based on P792 data no correlation between tumor microvascular characteristics and histologic markers (SBR score or MVD) was found in this breast tumor model. Our analysis suggests that contrast media of relatively large (on the order of 90 kDa) molecular size, such as albumin-(GdDTPA)(30), are more accurate for the characterization of tumor microvessels.

Animals↗
PubMed2001

Coronary magnetic resonance angiography: experimental evaluation of the new rapid clearance blood pool contrast medium P792.

The signal-enhancing characteristics of a new monodisperse monogadolinated macromolecular MR contrast medium (P792) were evaluated for magnetic resonance angiography (MRA) of the coronary arteries. A total of 15 cardiac examinations were performed in pigs at 1.5 T using a 3D gradient-echo sequence. Images were acquired during breath-hold before and up to 35 min after IV injection of Gd-DTPA (0.3 mmol Gd/kg), Gd-BOPTA (0.2 mmol Gd/kg), and P792 (13 micromol Gd/kg). An increase in the signal-to-noise ratio (SNR) of 97% +/- 17%, 108% +/- 37%, and 109% +/- 31% in coronary arteries and of 82% +/- 19%, 82% +/- 24%, and 28% +/- 18% in myocardium, respectively, was measured during the first postcontrast acquisition. The blood-to-myocardium signal-difference-to-noise ratio (SDNR) was significantly higher for P792 than for the other Gd compounds (P <.05) for up to 15 min after injection. Qualitative assessment showed that visualization of the coronary arteries and their branches was significantly better for P792 compared to the low-molecular Gd compounds (P <.05). The blood pool contrast medium P792 is well suited for MRA of the coronary arteries.

Animals↗
PubMed2001

Comparison of plasma and peritoneal concentrations of various categories of MRI blood pool agents in a murine experimental pharmacokinetic model.

The aim of this study was to validate an experimental model designed to distinguish four categories of contrast agents, non specific agents (NDA, Gd-DOTA) characterized by rapid and total extravasation; low diffusion agents (LDA, P760) characterized by delayed extravasation; and rapid (P792) and slow clearance (P717) blood pool agents (BPA) characterized by limited extravasation. Plasma and peritoneal gadolinium concentrations were simultaneously measured after intravenous injection of various contrast agents in mice. Products of each category were compared in this model.The plasma pharmacokinetic profiles were similar for Gd-DOTA and P760 (t1/2=13.3 and 13.8 min, respectively), whereas the half-lives were 22 and 1212 min for P792 and P717, respectively. The plasma clearance was inversely related to the size of the contrast agent. The intraperitoneal diffusion patterns of the various products were related to the molecular volume: C(max) per dose decreased progressively (78.7, 51.2, 44.2, 33.5 1/l) and t(max) increased (7, 15, 40, and 120 min) for Gd-DOTA, P760, P792 and P717, respectively. Nevertheless, the same quantities of Gd-DOTA and P760 (AUC ratio of 78.4 and 76.8, respectively) diffused into the peritoneum, whereas only 44.5% of P792 and 21.5% of P717 extravasated.The data obtained in this peritoneal permeability model with the various categories of contrast agents provide an estimation of the quantities of contrast agents diffusing into a permeable interstitium and may be used to predict the corresponding signal intensity, which can be measured locally.

Animals↗
PubMed2001

P792: a rapid clearance blood pool agent for magnetic resonance imaging: preliminary results.

An original MRI contrast agent, called P792, is described. P792 is a gadolinium macrocyclic compound based on a Gd-DOTA structure substituted by hydrophilic arms. The chemical structure of P792 has been optimized in order to provide (1) a high r(1) relaxivity in the clinical field for MRI: 29 mM(-1)xs(-1) at 60 MHz, (2) a high biocompatibility profile and (3) a high molecular volume: the apparent hydrodynamic volume of P792 is 125 times greater than that of Gd-DOTA. As a result of this high molecular volume, P792 presents an unusual pharmacokinetic profile, as it is a Rapid Clearance Blood Pool Agent (RCBPA) characterized by limited diffusion across the normal endothelium. The original pharmacokinetic properties of this RCBPA are expected to be well suited to MR coronary angiography, angiography, perfusion imaging (stress and rest), and permeability imaging (detection of ischemia and tumor grading). Further experimental imaging studies are ongoing to define the clinical value of this compound.

Animals↗
PubMed2001

Carboxymethyldextran-A2-Gd-DOTA enhancement patterns in the abdomen and pelvis in an animal model.

The aim of this study was to assess MR signal enhancement patterns of carboxymethyldextran (CMD)-A2-Gd-DOTA, a new macromolecular contrast agent, in the abdomen and pelvis of New Zealand white rabbits. Nine New Zealand white rabbits underwent MRI before and following injection of 0.05 mmol/kg body weight (bw) CMD-A2-Gd-DOTA (52.1 kDa), using turbo FLASH-, dynamic FLASH 60 degrees-, T1- and T2-weighted spin-echo and turbo spin-echo sequences up to 10 days p.i. Changes in blood and tissue signal intensities (deltaSI) and relaxation rates (deltaR1) were calculated. Differences between pre- and post-contrast MRI data were compared using the Scheffé test. CMD-A2-Gd-DOTA demonstrated significant blood-pool enhancement and significant tissue enhancement on T1-weighted images, whereas no significant signal changes were observed on T2-weighted images (P < 0.05). Kidney parenchyma, pelvis and bladder demonstrated a subsequent enhancement, resembling renal elimination of the majority of the contrast agent. Liver parenchyma demonstrated a slow, delayed decay of the contrast enhancement due to storage and biodegradation of larger subfractions of the contrast agent. All tissue signal intensities were back to baseline 10 days p.i. CMD-A2-Gd-DOTA is a new macromolecular contrast agent with blood-pool effect, significant signal enhancement of abdominal organs and pelvic bone marrow, partial storage in the liver and baseline tissue signal intensities by 10 days p.i.

Abdomen↗
PubMed2001

Preclinical profile of the monodisperse iodinated macromolecular blood pool agent P743.

RATIONALE AND OBJECTIVES: To summarize the chemical synthesis, physicochemical characterization, pharmacokinetic behavior, and biological evaluation of P743, a new macromolecular iodinated contrast medium. METHODS: The synthesis and molecular modeling of the iodinated macromolecule P743 are described. The pharmacokinetic profile was established in rabbits and rats. Acute toxicity in mice, renal tolerance in normal rabbits, and renal tolerance in uninephrectomized, dehydrated rats undergoing selective intrarenal injection was evaluated. In vitro permeability effects on isolated mastocytes and on the coagulation pathways were carried out. Computed tomography vascular imaging was performed after intravenous injection of P743 (300 mg I/kg) in rabbits and compared with the nonspecific nonionic agent iobitridol. RESULTS: P743 is a monodisperse, macromolecular iodinated contrast medium. In both rabbits and rats, P743 showed a pharmacokinetic profile consistent with that of a rapid-clearance blood-pool agent. Its diffusion through the endothelium was found to be low in vitro, thus confirming early confinement of this macromolecule, unlike nonspecific contrast media. In both species, P743 was excreted by glomerular filtration. Acute toxicity disclosed no mortality at the highest volume that could be injected into mice, leading to a median lethal dose greater than 8.9 g I/kg. Renal tolerance was found to be good in both euvolemic rabbits and uninephrectomized, dehydrated rats. No histamine or leukotriene B4 release was found on RBL-2H3 isolated mastocytes. P743 did not interfere with the coagulation pathways. Imaging experiments confirmed that P743 remains in the vascular compartment for a longer time than does iobitridol, thus allowing vascular enhancement that is twice as high as that of iobitridol in the recirculation phase. CONCLUSIONS: The pharmacokinetic and imaging profiles of P743, a new, monodisperse, macromolecular blood-pool iodinated contrast medium, were consistent with those of a rapid-clearance blood-pool agent. Its initial safety profile is satisfactory. Further experimental imaging studies are required to define the clinical interest in such molecules.

Animals↗
PubMed2001

Physicochemical and biological evaluation of P792, a rapid-clearance blood-pool agent for magnetic resonance imaging.

RATIONALE AND OBJECTIVES: To summarize the physicochemical characterization, pharmacokinetic behavior, and biological evaluation of P792, a new monogadolinated MRI blood-pool agent. METHODS: The molecular modeling of P792 was described. The r1 relaxivity properties of P792 were measured in water and 4% human serum albumin at different magnetic fields (20, 40, 60 MHz). The stability of the gadolinium complex was assessed. The pharmacokinetic and biodistribution profiles were studied in rabbits. Renal tolerance in dehydrated rats undergoing selective intrarenal injection was evaluated. Hemodynamic safety in rats and in vitro histamine and leukotriene B4 release were also tested. RESULTS: The mean diameter of P792 is 50.5 A and the r1 relaxivity of this monogadolinium contrast agent is 29 L x mmol(-1) x s(-1) at 60 MHz. The stability of the gadolinium complex in transmetallation is excellent. The pharmacokinetic and biodistribution profiles are consistent with that of a rapid-clearance blood-pool agent: P792 is mainly excreted by glomerular filtration, and its diffusion across normal endothelium is limited. Renal and hemodynamic safety is comparable to that of the nonspecific agent gadolinium-tetraazacyclododecane tetraacetic acid. No histamine or leukotriene B4 release was found in RBL-2H3 isolated mastocytes. CONCLUSIONS: The relaxivity of P792 at clinical field is very high for a monogadolinium complex without protein binding. The pharmacokinetic and biodistribution profiles are consistent with those of a rapid-clearance blood-pool agent. Its initial safety profile is satisfactory. Experimental and clinical studies are underway to confirm the potential of P792 in MRI.

Acute Kidney Injury↗
PubMed2001

CT pulmonary angiography with a macromolecular contrast medium: a comparative study versus iobitridol in rabbits.

RATIONALE AND OBJECTIVES: To compare the pharmacokinetics of a new macromolecular iodinated contrast medium, prototype P743, with a standard contrast agent (iobitridol) for spiral computed tomography pulmonary angiography in rabbits. METHODS: Manual injection was first used to test the performance of P743 even in cases of nonoptimal bolus timing. Then a protocol was designed to compare vessel enhancement in both first-pass and delayed scans for the two contrast agents with the help of a power injector. RESULTS: With manual fast injection, the first pass of iobitridol was observed only on proximal scans. Conversely, opacification of vessels was maintained during three spiral scans with P743 under the same injection conditions. When optimal bolus timing was performed, higher vessel enhancement was observed during bolus first pass with iobitridol (iodine dosage 250 mg I/kg) compared with P743 (150 mg I/kg). However, during the postbolus phase, the decrease in attenuation values was markedly faster with iobitridol than with P743. CONCLUSIONS: This study confirmed that P743 remains more intravascular than iobitridol, which may have clinical implications for the diagnosis of pulmonary embolism, for example.

Angiography↗
PubMed2001

Interstitial MR lymphography with a conventional extracellular gadolinium-based agent: assessment in rabbits.

PURPOSE: To evaluate gadoterate meglumine as a contrast agent for interstitial magnetic resonance (MR) lymphography in combination with an adapted fast three-dimensional (3D) MR sequence. MATERIALS AND METHODS: In 12 New Zealand White rabbits, 0.5 mL of undiluted gadoterate meglumine was injected subcutaneously into the dorsal foot pad (n = 9) or the foreleg (n = 3) bilaterally. Immediately after administration, a slight massage was performed at the injection site. Imaging was performed with a 3D spoiled gradient-recalled echo sequence (6.7/1.6 [repetition time msec/echo time msec]; field of view, 28.0 x 19.6; two signals acquired) similar to that used for 3D MR angiography. Thus, 3D maximum intensity projection images could be obtained. Images were obtained before injection and 5, 15, 30, 60, and 120 minutes after injection. RESULTS: In the hind legs, as many as four successive lymph node groups were depicted with maximum enhancement after 5-15 minutes for the popliteal lymph node group, 15-30 minutes for the inguinal lymph group, and 30-60 minutes for the iliac-paraaortal lymph node group; the iliac-paraaortal lymph node group was not consistently enhanced. In the forelegs, four successive lymph node groups, including axillary and mediastinal lymph node groups, showed marked gadolinium uptake, with maximum enhancement 5-15 minutes after injection. CONCLUSION: As a widely tested positive-enhancing T1 contrast agent with favorable safety features, gadoterate meglumine allows the depiction of three to four successive lymph node groups early after subcutaneous injection. With the sequence used, 3D MR lymphangiograms can be obtained.

Animals↗
PubMed2000

Physical, chemical, and biological evaluations of P760: a new gadolinium complex characterized by a low rate of interstitial diffusion.

An original gadolinium chelate, termed P760, which diffuses through the vascular endothelium but at a much lower rate than nonspecific agents (NSA), is described. P760 is a gadolinium macrocyclic compound based on a DOTA structure that is substituted by hydrophilic bulky groups branched on the amino-carboxylic residues. The molecular weight is 5293, and the molecular volume, measured by light scattering, is 30 times higher (11.5 nm3) than that of gadolinium (Gd)-DOTA (0.38 nm3). The increase in molecular volume and weight has two consequences: a) higher relaxivity (r1; 24.7 mM-1.s-1 compared with 3.4 mM-1.s-1 for Gd-DOTA at 20 Mhz, 37 degrees C); and b) a lengthening of its transport rate through the endothelium. P760 presents a peculiar pharmacokinetic profile: at early times post injection, the blood concentrations are higher than those of Gd-DOTA, but after 20 minutes, the blood concentrations are equal for the two compounds. The body clearances of the products are identical (i.e., glomerular filtration rate). P760 molecules are large enough to have a restricted diffusion through the endothelium but, conversely, small enough to pass freely through the glomerular membrane. This limited extravasation has been observed in rabbits by magnetic resonance angiography or in investigations of tumor permeability. Further experimental imaging studies are needed to define the clinical interest of such properties.

Animals↗
PubMed2000

Kinetic characterization of CMD-A2-Gd-DOTA as an intravascular contrast agent for myocardial perfusion measurement with MRI.

Recent developments in magnetic resonance imaging (MRI) using specific contrast media allow the assessment of myocardial perfusion. The purpose of this study was to characterize the intravascular properties of a new macromolecular contrast agent, CMD-A2-Gd-DOTA, to evaluate myocardial perfusion. Two groups of isolated pig hearts perfused at various controlled flows were used. To demonstrate the intravascular properties of CMD-A2-Gd-DOTA, the agent was simultaneously injected with 99mTc-labeled red blood cells in five hearts (group 1). Tracer kinetics of both compounds were assessed by coronary sinus effluent sampling, radioactivity counting and concentration determination in samples for first-pass time curves measurements. Five other hearts (group 2) were studied using a two-slice turboFLASH sequence on a 1.5-T whole-body MRI in order to evaluate first-pass CMD-A2-Gd-DOTA signal intensity (SI) versus time curves. In group 1, for the studied flows ranging from 0.8 to 3.1 ml/min(-1) x g(-1), CMD-A2-Gd-DOTA showed first-pass concentration curves typical of an intravascular contrast agent. In group 2, MRI parameters, i.e., upslope and mean transit time of SI time curves correlated strongly with myocardial perfusion. Within the physiologic range of flows, CMD-A2-Gd-DOTA was able to demonstrate tracer kinetics for in vivo assessment of myocardial perfusion using MRI.

Animals↗
PubMed2000

Pilot MR evaluation of pharmacokinetics and relaxivity of specific blood pool agents for MR angiography.

RATIONALE AND OBJECTIVES: To evaluate the use of two new blood pool contrast agents (P760, P775) compared with a low-molecular-weight gadolinium chelate in MR angiography. METHODS: The r1 efficiency of P760 was evaluated in vitro at 1.5 T; 3D abdominal contrast-enhanced MR angiography with qualitative analysis was compared in four rabbits after injection of incremental doses of P760 and in one rabbit after Gd-DOTA. A dynamic MR study was performed using a 2D T1-weighted turbo-flash MR sequence after injection of P760, P775, and Gd-DOTA. Each compound was tested at equivalent doses in three rabbits to assess r1 efficiency. Quantitative analysis of signal intensity in the aorta, the inferior vena cava, the renal cortex, and the medulla was performed. RESULTS: In vitro, the r1 efficiency of P760 was 23.3 mmol(-1) x L x sec(-1) at 1.5 T. Injection of a dose of P760 10 times less than Gd-DOTA allowed similar vessel visualization. The signal intensity peak and first-pass contrast kinetics in the aorta and the inferior vena cava were similar with the three products. Compared with P760 and Gd-DOTA, P775 allowed a greater renal cortex signal intensity at the first pass and a faster decrease on delayed images. CONCLUSIONS: The superior r1 efficiency of P760 and P775 was confirmed in vitro and in vivo at 1.5 T compared with Gd-DOTA, and P775 proved to be a rapid-clearance blood pool agent.

Animals↗
PubMed2000

Pharmacokinetics of three gadolinium chelates with different molecular sizes shortly after intravenous injection in rabbits: relevance to MR angiography.

RATIONALE AND OBJECTIVES: To mimic an MR angiographic protocol, an experimental model was developed in rabbits to determine gadolinium concentrations in blood early after injection. Contrast agents with different molecular sizes were compared. METHODS: The influence of injection parameters (injection rate, duration of injection, volume of injection, dose) was assessed, and two blood pool agents (P760, P717) were compared with the low-molecular-weight Gd-DOTA under similar conditions. RESULTS: Two main phases were identified: bolus and post-bolus. Injection parameters strongly influenced the pattern of the bolus phase, but the postbolus phase was sensitive only to the injected dose. The blood pool agents presented a bolus phase profile similar to that of Gd-DOTA, but 45 seconds after injection, 84% of P717 molecules were still present in the blood compartment, compared with 65% of P760 molecules and only 51% of Gd-DOTA molecules. CONCLUSIONS: Blood pool agents are useful for MR angiographic protocols involving the postbolus phase. In protocols in which only the bolus phase is imaged, blood pool agents provide similar data to Gd-DOTA, provided that the injection rate, iso-T1 efficiency dose, and volume are similar.

Animals↗
PubMed1999

P760 and P775: MRI contrast agents characterized by new pharmacokinetic properties.

RATIONALE AND OBJECTIVES: In this paper we discuss novel MR imaging blood pool agents characterized by new pharmacokinetic properties. METHODS: The pharmacokinetics of the products were studied in a rabbit model. The potential of these new products was demonstrated in experimental MR imaging. RESULTS AND CONCLUSION: Three main classes of blood pool agents have been defined and characterized according to their pharmacokinetic properties: low diffusion agents, rapid clearance blood pool agents, slow clearance blood pool agents. Each kind of blood pool agent is expected to have different diagnostic applications.

Animals↗