Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent.

Rationale And Objectives: Gadomer-17 is a new magnetic resonance (MR) contrast medium presently in clinical development. It is a dendritic gadolinium (Gd) chelate carrying 24 Gd ions. This study investigated the pharmacokinetic behavior of this contrast medium.

Rapid multimethod for verification and determination of toxic pesticides in whole blood by means of capillary GC-MS.

A rapid and single multimethod was developed to determine substances of different pesticide classes in whole blood in the event of acute human intoxications, as required by EU Commission Directive 96/46. The method was validated by an in-house and an independent laboratory validation. Whole blood is hemolyzed and then deproteinized.

Gadopentetate dimeglumine excretion into human breast milk during lactation.

Purpose: To analyze the amount of gadopentetate dimeglumine excreted into human breast milk following intravenous injection of a clinical dose.

Materials And Methods: Gadopentetate dimeglumine was injected intravenously in 20 lactating women (23-38 years of age). Breast-feeding was interrupted for at least 24 hours.

Is absolute noninvasive temperature measurement by the Pr[MOE-DO3A] complex feasible.

Recently, the feasibility of the praseodymium complex of 10-(2-methoxyethyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7-tr iacetate (Pr[MOE-DO3A]) for non-invasive temperature measurement via 1H spectroscopy has been demonstrated. Particularly the suitability of the complex for non-invasive temperature measurements including in vivo spectroscopy without spatial resolution as well as first spectroscopic imaging measurements at low temporal resolution (> or = 4 min) and high temporal resolution (breath hold, approximately 20 s) has been shown. As of today, calibration curves according to the particular experimental conditions are necessary.

Non-invasive MR thermometry by 2D spectroscopic imaging of the Pr[MOE-DO3A] complex.

Future progress in regional hyperthermia requires a practical method for non-invasive thermometry. In magnetic resonance tomography, spin density, T1 relaxation time, diffusion coefficient and proton resonance frequency are candidates to measure temperature distributions. When used clinically in the pelvic region, all these methods are compromized by artifacts arising from different tissues, tissue alterations under hyperthermia, physiological and random movements, inhomogeneities, drift phenomena, and field instabilities.

Magnetic iron oxide particles coated with carboxydextran for parenteral administration and liver contrasting. Pre-clinical profile of SH U555A.

Rationale And Objectives: To evaluate the physical and pharmacological profiles of SH U555A, a suspension of magnetic iron oxide particles that is designed to enhance the visualization of liver tumors and metastases.

Material And Methods: Chemical and physical methods were used to characterize the size and structure of these magnetic iron oxide particles in aqueous solution. The biodistribution and pharmacokinetics of the particles were studied in mice, rats and dogs.

[Thermometry by measuring the chemical shift of lanthanide complex].

Background: In the long-term, non-invasive thermometry is vital for the continued clinical and technological development of regional hyperthermia. In magnetic resonance tomography. T1 relaxation time, diffusion and proton resonance frequency are used to measure temperature distributions.

Noninvasive temperature measurement in vivo using a temperature-sensitive lanthanide complex and 1H magnetic resonance spectroscopy.

A new lanthanide complex, praseodymium-2-methoxyethyl-DO3A, was tested as a temperature indicator for 1H magnetic resonance spectroscopy under in vivo conditions, using a 2-T imaging system. The chemical shift of the methoxy group of the compound is strongly temperature dependent. In vitro, a shift change of -0.

Pre-clinical evaluation of gadobutrol: a new, neutral, extracellular contrast agent for magnetic resonance imaging.

The Gd(3+)-complex of 10-(2,3-dihydroxy-1-hydroxymethylpropyl)-1,4,7,10-tetraazacyclo dodecane-1,4,7-triacetic acid(gadobutrol) is a new, neutral Gd-chelate for use as an extracellular contrast agent in magnetic resonance imaging (MRI). The blood level in dogs after intravenous (i.v.

Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging.

Purpose: To determine the safety, pharmacokinetics, and magnetic resonance (MR) imaging results of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) as a contrast agent for use in hepatobiliary MR imaging.

Materials And Methods: Gd-EOB-DTPA was tested at doses of 10, 25, 50, and 100 mumol per kilogram of body weight. Results of laboratory tests, clinical measurements, and pharmacokinetic data were obtained in 44 healthy volunteers in a double-blind, randomized, placebo-controlled design.

Comparison of iopamidol and ioversol in vitro and in animal studies.

In the present series of studies we investigated differences in vitro and in animal experiments between iopamidol (Iopamiron, CAS 60166-93-0) and ioversol (CAS 87771-40-2). The studies included the in vitro investigations partition coefficient, lysozyme inhibition, coagulation time and erythrocyte morphology as well as the in vivo paradigms acute toxicity, neural toxicity, general behavior/locomotor activity and angiography. Iopamidol was superior to ioversol in most of the tests.

Characterization of a gadolinium-labeled cholesterol derivative as an organ-specific contrast agent for adrenal MR imaging.

The purpose of the study was to determine if derivatization of cholesterol with a paramagnetic label could result in an organ-specific contrast agent for magnetic resonance imaging of the adrenal glands. Gadolinium-DO3A-labeled cholesterol was synthesized and the relaxivities in water and blood plasma determined at 0.47 T and 40 degrees C.

Preclinical testing of iopromide. 1st communication: pharmacological evaluation.

Pharmacological and pharmacokinetic characteristics of the non-ionic monomeric X-ray contrast agent iopromide (Ultravist, CAS 73334-07-3) were evaluated in preclinical studies. The scope of investigations included in vitro tests such as the determination of protein binding, the inhibition of complement, lysozyme, urokinase, platelet aggregation, the release of histamine, the influence on thromboplastin time. In vivo studies included bleeding time in rat, neural tolerance after intracisternal injection or administration into the carotid artery.

Contrast-enhanced MR imaging of liver and spleen: first experience in humans with a new superparamagnetic iron oxide.

The aim of this prospective study was to obtain the first human safety and magnetic resonance (MR) imaging results with a new formulation of superparamagnetic iron oxide (SPIO) (SHU 555 A). The SPIO was tested at four iron doses, from 5 to 40 mumol/kg. Laboratory tests and clinical measurements were done in 32 healthy volunteers for up to 3 weeks after administration.

Pharmacokinetics, dose proportionality, and tolerability of gadobutrol after single intravenous injection in healthy volunteers.

Rationale And Objectives: Gadobutrol is a new gadolinium-based hydrophilic and neutral macrocyclic contrast medium for magnetic resonance imaging. In this article, the authors report on the first application of gadobutrol in humans, up to a dose of 0.5 mmol/kg.

Pharmaceutical properties, biodistribution, and imaging characteristics of manganese-mesoporphyrin. A potential hepatobiliary contrast agent for magnetic resonance imaging.

Objectives: Manganese (III) mesoporphyrin (Mn-mesoporphyrin) was investigated for its pharmaceutical properties and magnetic resonance imaging characteristics as a potential hepatobiliary contrast agent.

Methods: Solubility, partition coefficient, plasma binding, proton relaxation enhancement, biodistribution, biliary excretion, liver extraction ratio, and liver enhancement were measured in various in-vitro and in-vivo systems.

Results: Mn-mesoporphyrin was soluble and stable at moderate alkaline pH in phosphate buffer.

Biliary excretion and pharmacokinetics of a gadolinium chelate used as a liver-specific contrast agent for magnetic resonance imaging in the rat.

The introduction of a lipophilic moiety into the gadolinium chelate Gd-DTPA (dimeglumine gadopentetate, Magnevist) yielded Gd-EOB-DTPA (short form), which has potential as a magnetic resonance contrast agent for liver mass screening. The pharmacokinetics of Gd-EOB-DTPA in rats is nonlinear because after correction for the 10-fold difference in dose, the area under the curve of plasma concentration versus time from time zero to infinity after single intravenous application of two different doses were not superimposable, and the amounts excreted renally and extrarenally differed significantly. However, for both dose groups tested, the values of renal clearance (9.

Pharmacokinetics in rats, dogs and monkeys of a gadolinium chelate used as a liver-specific contrast agent for magnetic resonance imaging.

The introduction of the lipophilic moiety, ethoxybenzyl, into the gadolinium chelate dimeglumine gadopentetate (Gd-DTPA, Magnevist, CAS 86050-77-3) yielded (4S) 4-(4-ethoxybenzyl)-3,6,9-tris (carboxylatomethyl)-3,6,9-triazaundecandioic acid, gadolinium complex, disodium salt (Gd-EOB-DTPA), a compound with a potential as a magnetic resonance contrast agent for liver mass screening. Both in the rat and in the dog the pharmacokinetics of Gd-EOB-DTPA were nonlinear in the dose range of 0.05-0.

A new lipophilic gadolinium chelate as a tissue-specific contrast medium for MRI.

Gd-Ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a highly water-soluble paramagnetic contrast agent. Due to its protein binding of about 10% and its lipophilic residue, Gd-EOB-DTPA exhibits both renal (30% of the dose) and hepatobiliary (70%) excretion in rats. Despite its lipophilic character, the compound displays a low toxicity (LD50 = 7.

In vivo and in vitro evaluation of Gd-DTPA-polylysine as a macromolecular contrast agent for magnetic resonance imaging.

Polylysine covalently linked to moieties of gadopentetate (Gd-DTPA), for use as a macromolecular blood pool marker for contrast material-enhanced magnetic resonance imaging (MRI), was characterized by means of physicochemical measurements and pharmacokinetics in rats and rabbits and compared with Gd-DTPA. Gd-DTPA-polylysine was composed of a series of polymers of different molecular sizes that on average were labeled with 60 to 70 Gd-DTPA moieties (average molecular weight, 48,700 daltons [D]). For the macromolecular compound Gd-DTPA-polylysine, relaxivity was three times higher than that of Gd-DTPA.

Formation of 2-methyltryptophan in the biosynthesis of thiostrepton: isolation of S-adenosylmethionine:tryptophan 2-methyltransferase.

L-2-Methyltryptophan was found to be an intermediate in the biosynthesis of the antibiotic thiostrepton. It was isolated from growing cultures and resting cells of Streptomyces laurentii in trapping experiments after the application of labeled L-methionine or L-tryptophan. Its formation from L-tryptophan and S-adenosylmethionine was studied in a cell-free extract of S.