Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.

Abstract: Haloaryl compounds are lithiated and thereafter metalated with one of the following organometallic groups: Sn(n-Bu).sub.3 or SnMe.sub.3. The resulting aryltin compound can be transmetalated in site-specific reaction with one of the following organometallic groups: HgX, Hg(OAc).sub.2, BX.sub.3, or BZ.sub.2, wherein X is Cl, Br, or I, and Z is alkyl or alkoxy. The metalated compounds are subsequently radiohalogenated via a demetalation reaction. A functional group suitable for conjugation to protein can be added subsequent or preferably prior to the radiohalogenation.Also compounds of the formula: R.sub.1 -Ar-R.sub.2, wherein R.sub.1 is either a radiohalogen or any one of the organometallic groups stated above, Ar is aromatic or heteroaromatic ring, and R.sub.2 is a short-chain substituent that does not activate the aromatic ring and that bears a functional group, or a precursor thereof, suitable for conjugation to protein under conditions that preserve the biological activity of the protein.

Abstract: Anchimeric chelates are disclosed which are capable of rapidly forming stable chelates with radionuclide metals at or below physiological temperature. Bifunctional anchimeric chelates having these same properties are also disclosed which are useful for radiolabeling target specific molecules such as monoclonal antibodies and fragments thereof.

Abstract: The present invention provides conjugates formed from calcified tissues targeting agents and radiolabeled compounds. One such conjugate comprises a chelate and a targeting agent that is capable of associating with calcified tissue, wherein the chelate contains at least one nitrogen atom or at least one sulfur atom or combinations thereof as the donor atoms.Another aspect of the invention provides method for using the conjugates for diagnostic and therapeutic purposes, including those related to bone cancer.

Abstract: Novel labeling reagents are useful for radiolabeling proteins such as antibodies with radionuclide metals such as .sup.99m Tc, .sup.186 Re, and .sup.188 Re. The reagents are of the following formula: ##STR1## wherein: each X is independently chosen from O, S, NH, or NR.sub.2, wherein R.sub.2 is a protecting group or an electron withdrawing group;R.sub.1 represents a protecting group, wherein each R.sub.1 is a separate protecting group or the two R.sub.1 symbols are taken together to represent a single protecting group; andeach T is independently chosen from hydrogen, lower alkyl groups of from 1 to about 6 carbon atoms, electron withdrawing groups, and lower alkyl groups of from 1 to about 6 carbon atoms substituted with electron withdrawing group(s).

Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.

Abstract: A process for reducing the non-target organ accumulation of immunoconjugates administered in vivo during therapeutic or diagnostic procedures involves the use of immunoconjugates comprising linkers that are cleavable at the non-target organs. The linkers are cleavable under conditions present, or induced, at one or more non-target organs, which include the kidneys or the liver.

Abstract: Covalently-linked complexes (CLCs) for targeting a defined population of cells, comprising a targeting protein; a cytotoxic agent; and an enhancing moiety, wherein the enhancing moiety is capable of promoting CLC-target cell interaction are disclosed. Methods for using the claimed CLCs to obtain enhanced in vivo cytotoxicity and enhanced in vivo imaging are also described.

Abstract: Chelating compounds of specific structure are useful for radiolabeling targeting proteins such as antibodies. The radiolabeled antibodies, or catabolites thereof, demonstrate improved biodistribution properties, including reduced localization within the intestines.

Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.

Abstract: There is disclosed an antibody and antibody-drug conjugate for targeting drug delivery as well as a class of chemicals, termed a drug-binding molecule of complementary structure (csDBM). The csDBM is designed to "fit" the drug by combining multiple non-covalent interactions between functional groups on the drug and opposing functional groups on the csDBM. The net result on the antibody-csDBM-drug conjugate is a drug stably bound to the csDBM so as not to dissociate during in vivo administration, but not so tightly bound to allow drug dissociation from the conjugate without significant loss of activity and retaining the drug's ability to bind to a higher affinity site on or within the target cell.

Abstract: Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy.

Abstract: The present invention provides conjugates formed from calcified tissues targeting agents and radiolabeled compounds. One such conjugate comprises a chelate and a targeting agent that is capable of associating with calcified tissue, wherein the chelate contains at least one nitrogen atom or at least one sulfur atom or combinations thereof as the donor atoms.Another aspect of the invention provides methods for using the conjugates for diagnostic and therapeutic purposes, including those related to bone cancer.

Abstract: The present invention provides metal chelating compounds, to chelates and chelate-targeting agent conjugates formed from the chelating compounds, and to methods for making and using these compositions. The chelating compounds incorporate two nitrogen atoms and three sulfur atoms ("N.sub.2 S.sub.3 "), two nitrogen atoms and four sulfur atoms ("N.sub.2 S.sub.4 "), or three nitrogen atoms and three sulfur atoms ("N.sub.3 S.sub.3 "). Metals, and metal oxides, capable of being chelated by the compounds include those that are radionuclides, such as .sup.99m Tc and .sup.186/188 Re.The targeting agent portion of the chelate-targeting agent conjugates provided includes antibodies, peptides, hormones, enzymes and biological response modifiers. Methods for making the conjugates are provided and encompass the addition of a metal, or metal oxide, to a chelating compound prior to attachment to a targeting agent as well as subsequent to the attachment.

Abstract: There is disclosed a process for minimally derivatizing a targeting protein with a radionuclide such that the predominant species of derivatized targeting protein contains one radionuclide group as a single radiolabeled ligand, and whereby the binding characteristics of the targeting protein are minimally affected. There is further disclosed ligands that can chelate a metal radionuclide or bind a halogen radionuclide while providing a means for separating radiolabeled ligand from unradiolabeled ligand.

Abstract: Haloaryl compounds are lithiated and thereafter metalated with one of the following organometallic groups: Sn(n-Bu).sub.3 or SnMe.sub.3. The resulting aryltin compound can be transmetalated in site-specific reaction with one of the following organometallic groups: HgX, Hg(OAc).sub.2, BX.sub.3, or BZ.sub.2, wherein X is Cl, Br, or I, and Z is alkyl or alkoxy. The metalated compounds are subsequently radiohalogenated via a demetalation reaction. A functional group suitable for conjugation to protein can be added subsequent of preferably prior to the radiohalogenation.Also compounds of the formula: R.sub.1 -Ar-R.sub.2, wherein R.sub.1 is either a radiohalogen or any one of the organometallic groups stated above, Ar is aromatic or heteroaromatic ring, and R.sub.2 is a short-chain substituent that does not activate the aromatic ring and that bears a functional group, or a precursor thereof, suitable for conjugation to protein under conditions that preserve the biological activity of the protein.

Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.

Abstract: The present invention provides metal chelating compounds, to chelates and chelate-targeting agent conjugates formed from the chelating compounds, and to methods for making and using these compositions. The chelating compounds incorporate two nitrogen atoms and three sulfur atoms ("N.sub.2 S.sub.3 "), two nitrogen atoms and four sulfur atoms ("N.sub.2 S.sub.4 "), or three nitrogen atoms and three sulfur atoms ("N.sub.3 S.sub.3 "). Metals, and metal oxides, capable of being chelated by the compounds include those that are radionuclides, such as .sup.99m Tc and .sup.186/188 Re.The targeting agent portion of the chelate-targeting agent conjugates provided includes antibodies, peptides, hormones, enzymes and biological response modifiers. Methods for making the conjugates are provided and encompass the addition of a metal, or metal oxide, to a chelating compound prior to attachment to a targeting agent as well as subsequent to the attachment.

Abstract: Chelated radionuclide compositions are provided for conjugation to polypeptides and carbohydrates. The resulting conjugates may be used in diagnosis and therapy. Chelating compounds are disclosed.

Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.