Mallinckrodt Medical, Inc.

Hemagen/pfc

Other

William P Cacheris

Linda Meeh

David H White

Steven R Woulfe

Dennis L Nosco

Edward A Deutsch

Robert G Wolfangel

Karen F Deutsch

William H Ralston

Janet B Wilking

Raymond C Grabiak

Youlin Lin

Thomas J Richard

Lynn A deLearie

Raghavan Rajagopalan

William L Neumann

Robert J Kaufman

Dennis A Moore

Muthunadar P Periasamy

Donald R VanDeripe

T Jeffrey Dunn

Max D Adams

Muthanadar P Periasamy

Jeffrey A Levine

Albert C Lee

Treated apatite particles are disclosed for enhancing medical diagnostic imaging such as magnetic resonance imaging ('MRI'), magnetic resonance spectroscopy ('MRS'), magnetic resonance spectroscopy imaging ('MRSI'), X-ray diagnostic imaging, and ultrasound imaging. Novel coating and manufacturing techniques are disclosed to control particle size and particle aggregation resulting in compositions for organ specific imaging of the liver, spleen, gastrointestinal tract, or tissue disease states is obtained. Depending on the diagnostic imaging technique, apatite particles are treated to be paramagnetic, radiopaque, or echogenic. The apatite particles may also be fluorinated to form stable fluoroapatite compositions useful for .sup.19 F imaging. Also disclosed are diagnostic compositions and methods of performing medical diagnostic procedures which involve administering to a warm-blooded animal a diagnostically effective amount of the above-described apatite particles and then performing the medical diagnostic procedure.

Treated apatite particles for medical diagnostic imaging

Emulsions of paramagnetic contrast agents, and processes of making and using them are disclosed. The emulsions contain water, a dispersed oil phase and a complex of a paramagnetic metal ion and an organic acid chelator, for example DTPA (diethylenetriaminepentaacetic acid), having a C.sub.10 -C.sub.30 saturated aliphatic group and an hydroxyl group bonded to the nitrogen atom. The emulsions are very stable and therapeutically acceptable for intravenous administration to enhance MRI imaging.

Paramagnetic complexes of N-alkyl-N-hydroxylamides of organic acids and

Treated apatite particles are disclosed for enhancing radical diagnostic imaging such as magnetic resonance imaging ('MRI'), magnetic resonance spectroscopy ('MRS'), magnetic resonance spectroscopy imaging ('MRSI'), X-ray diagnostic imaging, and ultrasound imaging. Novel coating and manufacturing techniques are disclosed to control particle size and particle aggregation resulting in compositions for organ specific imaging of the liver, spleen, gastrointestinal tract, or tissue disease states is obtained. Depending on the diagnostic imaging technique, apatite particles are treated to be paramagnetic, radiopaque, or echogenic. The apatite particles may also be fluorinated to form stable fluoroapatite compositions useful for .sup.19 F imaging. Also disclosed are diagnostic compositions and methods of performing medical diagnostic procedures which involve administering to a warm-blooded animal a diagnostically effective amount of the abovedescribed apatite particles and then performing the medical diagnostic procedure.

Treated apatite particles for ultrasound imaging

Treated calcium/oxyanion-containing particles are disclosed for enhancing medical diagnostic imaging such as magnetic resonance imaging ('MRI'), magnetic resonance spectroscopy ('MRS'), magnetic resonance spectroscopy imaging ('MRSI'), X-ray diagnostic imaging, and ultrasound imaging. Novel coating and manufacturing techniques are disclosed to control particle size and particle aggregation resulting in compositions for organ specific imaging of the liver, spleen, or tissue disease states is obtained. Depending on the diagnostic imaging technique, calcium/oxyanion-containing particles are treated to be paramagnetic, radiopaque, or echogenic. Also disclosed are diagnostic compositions and methods of performing medical diagnostic procedures which involve administering to a warm-blooded animal a diagnostically effective amount of the above-described particles and then performing the medical diagnostic procedure.

Treated calcium/oxyanion-containing particles for medical diagnostic

Emulsions of paramagnetic contrast agents, and processes of making and using them are disclosed. The emulsions contain water, a dispersed oil phase and a complex of a paramagnetic metal ion and an organic chelator having a C.sub.10 -C.sub.30 unsaturated aliphatic group. The emulsions are very stable and therapeutically acceptable for intravenous administration to enhance MRI.

Emulsions of paramagnetic contrast agents for magnetic resonance imaging

Methods of preparing solid apatite particles using a microfluidizer, for use in medical diagnostic imaging such as magnetic resonance imaging, X-ray, and ultrasound. The desired apatite particles are synthesized, passed through a microfluidizer, and purified to remove excess base, salts, and other materials used to synthesize the particles. The microfluidizer causes two high pressure streams to interact at ultra high velocities in a precisely defined microchannel. Microfluidization of preparations causes small (&lt;5 .mu.m) and uniform particles to be formed. Coating and purifying (especially by tangential flow filtration) the particles improves particle stability.

Microfluidization of radioactive calcium/oxyanion-containing particles

Treated apatite particles are disclosed for enhancing medical diagnostic imaging such as magnetic resonance imaging ('MRI'), magnetic resonance spectroscopy ('MRS'), magnetic resonance spectroscopy imaging (37 MRSI'), X-ray diagnostic imaging, and ultrasound imaging. Novel coating and manufacturing techniques are disclosed to control particle size and particle aggregation resulting in compositions for organ specific imaging of the liver, spleen, gastrointestinal tract, or tissue disease states is obtained. Depending on the diagnostic imaging technique, apatite particles are treated to be paramagnetic, radiopaque, or echogenic. The apatite particles may also be fluorinated to form stable fluoroapatite compositions useful for .sup.19 F imaging. Also disclosed are diagnostic compositions and methods of performing medical diagnostic procedures which involve administering to a warm-blooded animal a diagnostically effective amount of the abovedescribed apatite particles and then performing the medical diagnostic procedure.

Treated apatite particles for x-ray diagnostic imaging

Microfluidization of calcium/oxyanion-containing particles

Hybrid agents for enhancing in vivo diagnostic imaging of body organs and tissues, and methods of preparing and using the same.

Iodo-phenylated chelates for magnetic resonance imaging

Methods and compositions are disclosed for enhancing .sup.19 F magnetic resonance imaging which utilize .sup.19 F magnetic resonance contrast media having enhanced .sup.19 F relaxivity. Fluorine-containing compounds having enhanced .sup.19 F relaxation properties resulting from direct association with an unpaired spin are disclosed. The fluorine-containing compound is associated with the unpaired spin by covalent attachment of a stable free radical, by complexation of a fluorinated complexing agent with a paramagnetic metal ion, or by salt formation or charge neutralization of a paramagnetic ion.

19F magnetic resonance imaging agents which include a nitroxide moiety

Preparation of apatite particles for medical diagnostic imaging

Methods and compositions are disclosed for enhancing magnetic resonance imaging which utilize hydrophilic free radical compounds as magnetic resonance contrast media. Typical magnetic resonance contrast media within the scope of the present invention include stable hydrophilic free radicals having a hydrophilic moiety, such as polyhydroxyalkyl groups and heterocyclic amino-alcohols such as dihydroxypyrrolidine, dihydroxypiperidine, and trihydroxypiperidine, and a stable free radical moiety, such as a nitroxide, phenoxy, or phenoxazinyl free radical moiety.

Hydrophilic free radicals for magnetic resonance imaging

Methods and compositions are disclosed for enhancing magnetic resonance imaging and spectroscopy which utilize derivatives of the even-numbered carbon clusters, known as 'fullerenes.' Perfluorinated carbon clusters of the formula C.sub.n F.sub.m, wherein n is in the range from 30-100 and m.ltoreq.n, may be used for fluorine-19 imaging. Incorporating paramagnetic metal species into the carbon cluster cage improves fluorine and proton imaging.

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Florissant, MO, United States of America

William P Cacheris