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M Blau

Publications and source records attributed to M Blau.

At least 19 recordsLinked to original sources
PubMed1995

Contrast material-carrying liposomes: biodistribution, clearance, and imaging characteristics.

PURPOSE: To assess the biodistribution, clearance, and computed tomographic (CT) imaging characteristics of interdigitation-fusion (IF) liposomes that carry iotrolan in their aqueous phases. MATERIALS AND METHODS: Biodistribution and clearance of liposomes containing iotrolan produced with the IF method (IF vesicles) were assessed in rats. CT scans of rats and dogs were obtained after injection of IF vesicles at 100 and 250 mg of iodine per kilogram of body weight. RESULTS: A high initial uptake (63%-96% of the injected dose) was found in the liver and spleen. Liver elimination showed half-lives to be 12.9 days at 250 mg of iodine per kilogram, 10.9 days at 100 mg, and 8.7 days at 25 mg. At 250 mg of iodine per kilogram, the rats had an average of 96 HU of hepatic and 321 HU of splenic enhancement. The dogs had 116 HU of hepatic and 65 HU of splenic enhancement. CONCLUSION: IF liposomes have favorable biodistribution, clearance, and imaging characteristics as hepatosplenic contrast agents.

Animals↗
PubMed1993

Phosphonate-modified Gd-DTPA complexes. III: The detection of myocardial infarction by MRI.

The potential of a phosphonate-modified-Gd-DTPA for MR image enhancement of myocardial infarction has been demonstrated in imaging experiments on rats. The agent, 1-hydroxy-3-aminopropane-1,1-diphosphonate-modified-Gd-DTPA (Gd-DTPA-HPDP) accumulates in two models of myocardial infarction, (i.e., drug-induced diffusely infarcted whole hearts and in focal acute myocardial infarction from a left coronary artery ligation). The time course of the accumulation of the agent in the focal model of infarction and subsequent washout has also been followed in vitro. Results of this kinetics demonstrate that the agent first perfuses all normal fluid spaces and then slowly diffuses into the occluded zone where it is retained for a prolonged period, in sufficient quantities to be useful as an MRI contrast agent. Wash-out of the agent from normal myocardium is fast and complete with MR signal returning to background in minutes. The specificity of Gd-DTPA-HPDP for soft-tissue calcification and its retention within the infarcts permitted imaging at 1 to 2 h postinjection, (after unbound material has cleared the normal tissues). Infarcted tissue appeared as regions of increased signal intensity in T1-weighted images (> 200% enhancement), and correlated with histopathology. Unmodified Gd-DTPA was not retained under identical conditions. Gd-DTPA-HPDP permits a more accurate infarct delineation than is possible with the unmodified agent.

Animals↗
PubMed1991

Phosphonate-modified GdDTPA complexes. I. NMRD study of the solution behavior of new tissue-specific contrast agents.

NMRD profiles, the magnetic field dependence of the water proton longitudinal relaxation rates, have been acquired for two new diphosphonate-modified GdDTPA complexes currently under evaluation as relaxation agents for the MRI detection of soft-tissue calcifications. Fresh dilute solutions show profiles identical to that of unmodified GdDTPA, which remain unchanged for up to 9 weeks. Solutions containing Gd species at MRI significant concentrations, 100 to 500 mM, show the presence of oligomers (n = 5 or more) upon aging, with much higher high-field relaxivities. Aggregation is attributed to the interactions between a gadolinium center and the phosphonate terminus of a neighboring molecule, and is prevented by esterification of the phosphonate terminus. Oligomers are also easily disrupted by dilution with phosphate-buffered saline, where the exogenous phosphate ions compete with the phosphonate. Other nucleophiles such as are present in protein side chains of bovine serum albumin also compete with the phosphonate in these associations, the result being species with even higher relaxivities.

Contrast Media↗
PubMed1991

Phosphonate-modified GdDTPA complexes. II. Evaluation in a rat myocardial infarct model.

The localization of 1-hydroxy-3-aminopropane-1,1-diphosphonate-modified GdDTPA (GdDTPA-HPDP) and 4-amino-butane-1,1-diphosphonate-modified GdDTPA (GdDTPA-BDP) in (1) normal and (2) infarcted rat hearts has been measured. The phosphonate-modified agents are preferentially retained in infarcted myocardium. The ratio of GdDTPA-HPDP accumulated in whole infarcted heart to that detected in normal heart is 15 at 2 hours after injecting a dose of 50 to 100 mumol/kg; the ratio is 2 for GdDTPA. At these doses, significant changes are detected in the tissue relaxation rates. An average relaxivity of 11.2 (mmol-sec)-1 is calculated for the agent in the infarcted whole heart. GdDTPA-BDP, in comparison, displayed prolonged blood retention. The result is a low diseased-to-normal heart ratio (approximately 2) at 2 hours, making this agent less attractive as a contrast agent.

Animals↗
PubMed1990

Biodistribution and clearance of contrast-carrying MREV liposomes.

Contrast-carrying liposomes (CCLs) have been shown to increase the attenuation coefficient of the liver and spleen during computed tomographic (CT) imaging. A modification of the reverse-phase evaporation preparative technique ("MREV") led to production of CCLs that entrap contrast media efficiently. After intravenous injection, MREVs are phagocytized by the Kupffer cells of the liver and the macrophages of the spleen. The biodistribution and clearance of MREVs were studied to evaluate their potential for clinical use, MREVs carrying iodine-125-iotrolan were administered intravenously to 12 rats at doses of 400 mg lipid (containing 400 mg iodine) per kilogram body weight. Pairs of rats were anesthetized and scanned at 3 hours, and 1, 7, 14, 27 and 48 days; CT attenuation values of liver, spleen, blood, kidneys and bladder were measured. Immediately following CT, the rats were killed and tissue specimens were radioassayed. Maximum iodine content in liver and spleen was reached at one day and sustained at high levels for seven days. Biologic removal half-time of the agent in both the liver and spleen was six days. Maximum CT enhancements over baseline were observed at 24 hours and reached 210 delta HU in the liver and 880 delta HU in the spleen per gram iodine injected per kilogram body weight. It is concluded that MREVs have appropriate imaging characteristics, biodistribution, and clearance to be effective CT contrast agents.

Animals↗
PubMed1990

Production and characterization of improved liposomes containing radiographic contrast media.

The authors have investigated liposomes prepared by the reverse-phase evaporation method (REVs) and a modification of this technique that employs a microemulsifier (MREVs), for the delivery of radiographic contrast media (RCM) to the liver and spleen. The modification entailed substituting a Microfluidizer (Microfluidics Inc., Newton, MA) for the sonication step of the REV technique. The MREV procedure is amenable to large-scale production and continuous-flow operation and yields products with high RCM encapsulation. Efficiently entrapped are ionic, high-osmolar diatrizoate (24.38 +/- 2.62% versus 8.35 +/- 0.55%; MREV versus REV), and nonionic, low osmolar Iotrolan (Schering AG, Berlin, FRG) (24.84 +/- 2.13% versus 7.25 +/- 1.19%) RCM with iodine-to-lipid ratio of 1.5:1. The MREV procedure, therefore, has practical advantages over the REV method. High liver and spleen uptakes of Iotrolan-containing vesicles were noted in normal rats. The diatrizoate MREVs lost their contents on contact with serum, resulting in urinary excretion of this agent. Computed tomography values of splenic and hepatic sections, 1 hour after intravenous injection of Iotrolan MREV (500 mgI/kg), are 0.78, and 0.08 Hounsfield Units (HU)/mgI/kg, respectively (versus 0.01, and 0.006 HU/mgI/kg for free Iotrolan).

Animals↗
PubMed1989

Development of phosphonate derivatives of gadolinium chelates for NMR imaging of calcified soft tissues.

We have synthesized several classes of gadolinium (Gd) complexes for use as NMR contrast agents in the detection of soft-tissue calcification. Class I was made up of strongly chelated GdDTPA complexes with one carboxylate arm coupled to a phosphonate-containing molecule through an amide link. Class II complexes were formed by Gd with several aminophosphonates and phosphono carboxylic acids. Class III were Gd complexes of weak chelates containing no phosphonate. The calcium-seeking ability of each complex was assessed by in vivo bone uptake. Tissue distribution in normal rats showed that only the complexes of GdDTPA modified with a diphosphonate group and GdEDTMP (EDTMP is ethylenediaminetetrakis(methylenephosponate] showed adequate bone localization at the concentrations required for NMR contrast enhancement (approximately 20% of a 100 mumol/kg dose).

Animals↗
PubMed1988

Preparation and biodistribution of [125I]IBZP: a potential CNS D-1 dopamine receptor imaging agent.

Carrier free [125I]IBZP, R-(+)-8-[125I] iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol), was prepared from the corresponding uniodinated compound by an oxidative iodination reaction with chloramine-T and sodium [125I]iodide. After purification by column chromatography the desired uptake was obtained with a high purity (greater than 95%). The agent showed good localization in brain after i.v. injection in rats, with an uptake of 2.7, 1.2 and 0.8% dose/organ at 2, 15 and 30 min post injection, respectively. The regional distribution in rat brain, as measured by in vivo autoradiography, displayed a high uptake in the caudate putamen, accumbens nucleus and substantia nigra, regions known to have a high concentration D-1 dopamine receptors. The uptake ratio of striatum/cerebellum increased with time; at 30 s and 2 h after injection the ratio was 1.1 and 5.3, respectively. The specific uptake in the D-1 dopamine receptor regions can be blocked by pretreatment with SCH-23390, a selective D-1 dopamine receptor antagonist (SCH-23390). The corresponding iodine-123 (t1/2 = 13 h, gamma energy 159 keV) labeled agent may be suitable for SPECT imaging of CNS D-1 dopamine receptors.

Animals↗
PubMed1988

Preparation and biodistribution of [125I]IBZM: a potential CNS D-2 dopamine receptor imaging agent.

A new CNS D-2 dopamine receptor imaging agent [125I]IBZM, (S)-3-[125I]-iodo-N-[(1-ethyl-2-pyrrolidinyl)] methyl-2-hydroxy-6-methoxybenzamide, was prepared by either an exchange reaction or by the chloramine-T method. After an i.v. injection, the agent easily passed through the blood-brain barrier and localized in the rat brain. At 2, 15, 30 and 60 min after the injection, the brain uptake was 2.9, 2.3, 1.8 and 0.7% dose/organ, respectively. Regional uptake ratio of striatum/cerebellum (target to nontarget ratio) increased from 1.4 at 30 s to 10.3 at 2 h after the i.v. injection. Digital autoradiography of rat brain sections showed high regional uptake in the caudate putamen and accumbens nucleus, areas known to have a high concentration of the D-2 dopamine receptor. The specific uptake at the D-2 dopamine receptor site was blocked by pretreatment with spiperone, a selective D-2 antagonist. When labeled with 123I (t1/2 = 13 h, 159 keV), [123I]IBZM may be useful for imaging the CNS D-2 dopamine receptor.

Animals↗
PubMed1988

Synthesis and biodistribution of 99mTc-labeled piperidinyl bis(aminoethanethiol) complexes: potential brain perfusion imaging agents for single photon emission computed tomography.

In developing clinically useful 99mTc-labeled radiopharmaceuticals for the evaluation of regional cerebral perfusion with single photon emission computed tomography (SPECT), a number of substituted alkyl(aryl)piperidinyl bis(aminoethanethiol) ligands for chelating [99mTc]TcO(III) were synthesized. Each ligand forms two diastereomers, syn and anti, after reacting with a racemic mixture of the ligand. The diastereomers were separated by high-pressure liquid chromatography. In biodistribution studies conducted in rats, the diastereomers exhibit widely disparate brain uptake values; however, this disparity seems to diminish as the steric bulk of the substituent at the C-4 position of the piperidinyl moiety increases. Furthermore, all the complexes evaluated failed to show a prolonged retention in the rat brain, suggesting that further structural modification may be necessary to obtain clinically useful complexes from this class of compounds.

Animals↗
PubMed1987

Comparison of [82Br]4-bromoantipyrine and [125I]4-iodoantipyrine: the kinetics of exchange reaction and biodistribution in rats.

Kinetics and mechanism of isotope exchange reaction between [82Br]bromide anion and 4-bromoantipyrine (BrAP), and the iodine-bromine exchange reaction between [125I]iodide anion and BrAP were studied. The preparation of [82Br]BrAP followed by exponential exchange law, the kinetics of the exchange reaction is a second-order reaction with an activation energy of 23.3 kcal/mol. The optimal exchange condition for halogen exchange between [125I]iodide and BrAP was by a hydrothermal melt method at 110 degrees C and 5 min reaction time. The partition coefficient at pH 7.0 for IAP and BrAP was 20.9 and 13.5, respectively. However, BrAP, which displayed the lower partition coefficient, showed higher brain uptake in rats than that for IAP (2.0% dose/organ vs 1.74% dose/organ), at 2 min after an i.v. injection.

Animals↗
PubMed1987

The production and evaluation of contrast-carrying liposomes made with an automatic high-pressure system.

An automatic, high-pressure system (Microfluidizer) has been found useful for producing contrast-carrying liposomes on an industrial scale. The goal of this investigation was to determine the feasibility of using this new microemulsification process to manufacture contrast-carrying microemulsified liposomes (MELs). Seven contrast media (three ionic, four nonionic) were encapsulated into the MELs. Light and electron microscopy, light scattering, radioisotope, and CT scan techniques were used to characterize these MELs, and the contrast entrapments among the studied media were compared. The contrast-carrying MELs had good properties for imaging normal reticuloendothelial tissues, selectively. They had a narrow size range (0.1-3.0 micron), a single bilayer wall, high liver and spleen upake, and low leakage rates. The nonionic media were significantly more effectively entrapped in the MELs than the ionic media (P less than .05). The iodine-to-lipid weight ratio was about 1:16 for ionic media and 1:4 for nonionic media. Physical properties of the contrast media such as osmotic pressure and charge appeared to affect contrast entrapment. It was concluded that the microemulsification process is a useful system for producing contrast-carrying liposomes continuously, on a large scale and in a reproducible manner.

Animals↗
PubMed1987

Effect of antidepressant and narcoleptic drugs on N-isopropyl p-iodoamphetamine biodistribution in animals.

N-isopropyl p-iodoamphetamine (IMP) demonstrates a high affinity for lung and brain during the first pass following intravenous injection. Its high brain affinity has been used to advantage for cerebral perfusion imaging, but the effects of drugs on IMP distribution could affect its utility. In this study, we determined the effects of the tricyclic antidepressant imipramine and the MAO inhibitors deprenyl and phenelzine on the biodistribution of IMP. We first determined the effect of loading dose and anesthesia on the biodistribution of IMP. In rats, biodistribution was not dependent on loading dose between 0.1 and 1.1 mg/kg. Anesthesia with thiopental and chloral hydrate depressed lung and brain IMP uptake. In rats, preloading doses of imipramine depressed lung uptake but did not result in increased brain IMP uptake; postloading doses of imipramine did not release IMP from the lung. In rabbits, simultaneous or postloading doses of imipramine resulted in release of IMP from the lung with an increase in brain activity. Both mixed A and B MAO inhibitors (phenelzine) and B selective MAO inhibitors (deprenyl) did not affect IMP distribution in rats. Based on the action of imipramine on IMP uptake and clearance in the lung, we postulate that IMP uptake and metabolism within the lung is related to the mixed function oxidase (MFO) system. As the lung is rich in the MFO system in humans, we would also predict from this study that IMP distribution in patients under antidepressant therapy would not be affected by either tricyclic or MAO inhibitor agents apart from the effect of these drugs on cerebral perfusion.

Amphetamines↗