Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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(R.sub.1)--?Y.sub.1 !.sub.n --(R.sub.2),(R.sub.1)--?Y.sub.1 --(R.sub.2)--Y.sub.1 !.sub.n --(R.sub.3)and(R.sub.1)--?Y.sub.1 --(R.sub.2)--Y.sub.2 !.sub.n --(R.sub.3)wherein the medically useful metal ion-binding domain is ?Y.sub.1 !.sub.n, ?Y.sub.1 --(R.sub.2)--Y.sub.1 !.sub.n or ?Y.sub.1 --(R.sub.2)--Y.sub.2 !.sub.n, in which n is a number between 1 and about 6 and Y.sub.1 and Y.sub.2 are amino acids with a sulfur, nitrogen or oxygen which is available for binding to metal ions, or can be made available for binding to metal ions; the biological-function domain is an amino acid sequence containing from 1 to about 20 amino acids located in any one or more of R.sub.1, R.sub.2 or R.sub.3 ; and those portions of R.sub.1, R.sub.2 and R.sub.

Abstract: 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(R.sub.1)--?Y.sub.1 !.sub.n --(R.sub.2),(R.sub.1)--?Y.sub.1 --(R.sub.2)--Y.sub.1 !.sub.n --(R.sub.3) and(R.sub.1)--?Y.sub.1 --(R.sub.2)--Y.sub.2 !.sub.n --(R.sub.3)wherein the medically useful metal ion-binding domain is ?Y.sub.1 !.sub.n, ?Y.sub.1 --(R.sub.2)--Y.sub.1 !.sub.n or ?Y.sub.1 --(R.sub.2)--Y.sub.2 !.sub.n, in which n is a number between 1 and about 6 and Y.sub.1 and Y.sub.2 are amino acids with a sulfur, nitrogen or oxygen which is available for binding to metal ions, or can be made available for binding to metal ions; the biological-function domain is an amino acid sequence containing from 1 to about 20 amino acids located in any one or more of R.sub.1, R.sub.2 or R.sub.3 ; and those portions of R.sub.1, R.sub.2 and R.sub.

Abstract: 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.

Abstract: 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.

Abstract: 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(R.sub.1)-[Y.sub.1 ].sub.n -(R.sub.2),(R.sub.1)-[Y.sub.1 -(R.sub.2)-Y.sub.1 ].sub.n -(R.sub.3)and (R.sub.1)-[Y.sub.1 -(R.sub.2)-Y.sub.2 ].sub.n -(R.sub.3)wherein the medically useful metal ion-binding domain is [Y.sub.1 ].sub.n, [Y.sub.1 -(R.sub.2)-Y.sub.1 ].sub.n or [Y.sub.1 -(R.sub.2)-Y.sub.2 ].sub.n in which n is a number between 1 and about 6 and Y.sub.1 and Y.sub.2 are amino acids with a sulfur, nitrogen or oxygen which is available for binding to metal ions, or can be made available for binding to metal ions; the biological-function domain is an amino acid sequence containing from 1 to about 20 amino acids located in any one or more of R.sub.1, R.sub.2 or R.sub.3 ; and those portions of R.sub.1, R.sub.2 and R.sub.

Abstract: 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.

Abstract: 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.

Abstract: 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 lympLICENSE RIGHTSThe U.S. Government has a paid-up license in this invention and the right in limited circumstances to require the patent owner to license others on reasonable terms as provided for by the terms of Small Business Innovative Research Grant No. 1 R43 AR41124 awarded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Department of Health and Human Services.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A kit for compounding radiolabeled monoclonal antibodies or antibody fragments for in vivo cancer diagnosis and therapy, which provides reagents for: (1) the selection of monoclonal antibodies or antibody fragments which are specific to a tumor specimen; (2) compounding the selected antibodies with a radionuclide material; and (3) quality control testing of the resulting compound. In the method of the invention, multiple aliquots of tumor biopsy material are fixed onto separate test areas of an apparatus which permits reaction with a panel of various monoclonal antibodies or antibody fragments known to react with tumor associated antigens. If one or more of the antibodies or antibody fragments bind to the tumor specimen, the reagents and antibodies or antibody fragments contained in the kit are combined with an appropriate, commercially available radionuclide.

Abstract: F(ab').sub.2 or Fab fragments of antibodies to: (a) human chorionic gonadotropin (hCG), hCG alpha subunit, hCG beta subunit, or an hCG-like material; or (b) other tumor specific or tumor associated molecules, to include carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), human melanoma associated antigens, human sarcoma associated antigens or other antigens, are radiolabeled with technetium-99m (Tc-99m). When the F(ab').sub.2 or Fab fragments of antibody to such tumor associated antigens are injected intravenously into a patient, the radiolabeled composition accumulates at tumor sites. The accumulation of the cancer seeking radiopharmaceutical at tumor sites permits detection by external gamma scintigraphy. Thus, the composition is useful in the monitoring, localization and detection of cancer in the body.In an alternative composition, a double antibody approach to tumor localization using radiolabeled F(ab').sub.2 or Fab fragments is utilized.

Abstract: Antibodies to human carcinoembryonic antigen (CEA), human alphafetoprotein (AFP) and/or to other anti-human tumor associated antigens (TAA) labeled with technetium-99m (Tc-99m) are administered to a human after the human has been administered anti-CEA, anti-AFP and/or other anti-TAAs, such as human melanoma-associated antigen, human neuroblastoma-associated antigen, human breast cancer-associated antigen, human ovary-associated antigen, human sarcoma-associated antigen, etc. The biodistribution of the labeled product composition accumulates at cancer sites, e.g., tumors that produce or express TAA, due to the affinity that the antibody has for the given tumor antigen. The accumulation at the tumor site(s) of a suitable amount of Tc-99m associated with the antibody allows detection via external scintigraphy and other means. Detection of the Tc-99m antibody composition by external scintigraphy permits localization and detection of tumors in vivo via a semi-noninvasive technique.

Abstract: 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 indefinitely stored frozen or lyophilized.

Abstract: 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.