Rhomed Incorporated

University Patents, Inc.

Nuc Med Inc.

Other

The University of New Mexico

Serono Laboratories, Inc.

Summa Medical Corporation

Buck A Rhodes

Paul O Zamora

David R Crockford

Scott W Burchiel

Shubh D Sharma

Paul L Mann

Jerry L Born

Dennis Eshima

Nicholas A Matwiyoff

Michael J Marek

Richard J Freer

David Torvestad

Frederick A Feuchter

The invention relates to radiotherapy with somatostatin-derived peptides labeled with medically useful metal ions. The invention in particular provides for methods and reagents for labeling somatostatin-derived peptides with perrhenate, in which a solution including somatostatin-derived peptide analogue containing at least one disulfide bond is provided, the solution is reacted with stannous ions and with a radioisotope, wherein the stannous ions are sufficient to substantially reduce the disulfide bonds of the peptide and the radioisotope, and the radiolabeled somatostatin-derived peptide analogue recovered. Also provided are methods for regional administration of radiolabeled somatostatin-derived peptides, methods for enhanced regional retention of radiolabeled somatostatin-derived peptides, methods for treatment of arthritis using radiolabeled somatostatin derived peptides, and methods for stabilizing radiolabeled somatostatin derived peptides.

Peptide radiopharmaceutical applications

Proteins containing one or more disulfide bonds or monosulfides are labeled with medically useful metal ions for use in diagnosis and treatment of a variety of pathologic conditions. Labeling is accomplished with a variety of metals, including radiometals, by using a reducing agent to reduce the disulfide bonds to thiolate groups; excess reducing agent, reaction by-products and any impurities are removed; and, a source of Sn (II) agent is added to the thiolate-containing protein. The resulting product may be stored frozen or lyophilized, with labeling accomplished by the addition of the medically useful metal ions.

Direct labeling of peptides with metal ions

Peptides containing a biological-function domain and a medically useful metal ion-binding domain are labeled with medically useful metal ions for use in diagnosis and treatment of a variety of pathologic conditions. The peptides have the amino acid sequence

Peptide-metal ion pharmaceutical preparation

High affinity linked, branched or linear repeat peptides containing two or more biological-function domains and at least one medically useful metal ion-binding domain are labeled with medically useful metal ions for use in a variety of diseases and pathologic conditions, including diagnosis and treatment of diseases. Such peptides include high affinity chemotactic peptides containing a biological-function domain which includes at least two linked N-formyl-MLF (SEQ. ID NO. 2) sequences and high affinity repeat and branched peptides containing two or more YIGSR (SEQ. ID NO. 1) sequences.

Polyvalent peptide pharmaceutical applications

Peptide-metal ion pharmaceutical labeling method

Methods and reagents for the in vivo tagging of leukocytes, and in particular lymphocytes, with a leukostimulatory agent and a linked medically useful metal ion, including a radioisotope, and subsequent detection of leukocyte or lymphocyte trafficking and sites of concentrated leukocytes or lymphocytes within the patient by radiodetection or paramagnetic means are disclosed.

Leukostimulatory agent for in vivo leukocyte tagging

Proteins containing one or more dtsulfide bonds or monosulfides are labeled with medically useful metal ions for use in diagnosis and treatment of a variety of pathologtc conditions. Labeling is accomplished with a variety of metals, including radiometals, by using a reducing agent to reduce the disulfide bonds to thiolate groups; excess reducing agent, reaction by-products and any impurities are removed; and, a source of Sn (II) agent is added to the thiolate-containing protein. The resulting product may be stored frozen or lyophilized, with labeling accomplished by the addition of the medically useful metal ions.

Direct labeling of antibodies and other protein with metal ions

Peptide-metal ion pharmaceutical preparation and method

Biomodulators, in conjunction with antibodies, tumor-specific agents or conjugates thereof, optionally linked to imaging-active moieties, can be administered to a host to enhance images thereof, e.g., NMR-, X-ray- or radioimages, preferably by increasing aberrant tissue signal intensity.

Enhancement of abnormal tissue uptake of antibodies, tumor-specific

Antibody against stage specific embryonic antigen-1 is radiolabeled by direct means with a radionuclide for use in detection of occult abscess and inflammation. Radiolabeling is accomplished by partial reduction of the disulfide bonds of the antibody using Sn(II), or using other reducing agents followed by the addition of Sn(II), removal of excess reducing agent and reduction by-products, and addition of a specified amount of radionuclide reducing agent, such as stannous tartrate. The resulting product may be store frozen or lyophilized, with radiolabeling accomplished by the addition of the radionuclide.

Direct radiolabeling of antibody against stage specific embryonic

Proteins containing one or more disulfide bonds are radiolabeled with radionuclides of technetium or rhenium for use in diagnosis and treatment of a variety of pathologic conditions. Radiolabeling is accomplished by partial reduction of the disulfide bonds of the protein using Sn (II), or using other reducing agents followed by the addition of Sn (II), removal of excess reducing agent and reduction by-products, and addition of a specified amount of pertechnetate or perrhenate reducing agent, such as stannous tartrate, with the addition accomplished in such a manner that further reduction of the protein is limited. The resulting product may be stored frozen or lyophilized, with radiolabeling accomplished by the addition of pertechnetate or perrhenate solution.

Direct radiolabeling of substrates containing monosulfides or disulfide

Methods and reagents for the in vivo tagging of leukocytes, and in particular lymphocytes with a leukostimulatory agent and a linked medically useful metal ion, including a radioisotope, and subsequent detection of leukocyte or lymphocyte trafficking and sites of concentrated leukocytes or lymp

In vivo lymphocyte tagging

A method is provided for rapidly determining the ability of sperm to undergo the acrosome reaction, using fluorescence microscopy, light microscopy or color change on a dot blot assay to determine the relative percentage of acrosome reacted sperm. Sperm are capacitated through use of bromelain or other enzymatic substances capable of capacitating sperm, with the total incubation time required to induce capacitation as little as fifteen minutes, yielding sperm that are fully capacitated and show excellent motility, with as many as 80% of normal sperm consistently induced to acrosome react.

Method for acrosome reaction assay

Proteins containing one or more disulfide bonds are radiolabeled with radionuclides of technetium or rhenium for use in diagnosis and treatment of a variety of pathologic conditions. Radiolabeling is accomplished by partial reduction of the disulfide bonds of the protein using Sn (II), or using other reducing agents followed by the addition of Sn (II), removal of excess reducing agent and reduction by-products, and addition of a specified amount of pertechnetate or perrhenate reducing agent, such as stannous tartrate, with the addition accomplished in such manner that further reduction of the protein is limited. The resulting product may be stored frozen or lyophilized, with radiolabeling accomplished by the addition of pertechnetate or perrhenate solution.

Direct radiolabeling of antibodies and other proteins with technetium or

Proteins are radiolabeled with radionuclides of technetium or rhenium by a process in which the disulfide bonds of the protein are first partially reduced with stannous salts or other disulfide reducing agents, all substances other than the desired reduced protein removed, by size exclusion chromatography or other purification means, and a specified, smaller amount of pertechnetate or perrhenate reducing agent, such as a stannous salt, is added to the reduced protein in a manner such that further reduction of the protein is limited. Pertechnetate or perrhenate is then added to the mixture of the reduced protein and the pertechnetate or perrhenate reducing agent; the pertechnetate or perrhenate is reduced and becomes strongly bonded to the protein via the sulfhydryl groups previously exposed by reduction of disulfide groups. The reduced protein and pertechnetate or perrhenate reducing agent can be idefinitely stored frozen or lyophilized.

Growing community of inventors

Albuquerque, NM, United States of America

Buck A Rhodes