Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. Biotinamido-N-methylglycyl-seryl-O-succinamido-benzyl DOTA is disclosed.

Abstract: Hepatic-directed compounds, reagents useful in making such compounds and associated methods and compositions are disclosed. Hepatic-directed compounds are processed by metabolic mechanisms, which generally differ in degree or in kind from the metabolic mechanisms encountered by compounds which are not so directed. Hepatic-directed compounds useful in the methods disclosed include a hexose cluster characterized by multiple hexose residues connected in an iteratively branched configuration. In one embodiment, the hexose cluster comprises at least four hexose residues with each branch of the configuration having two prongs. In another embodiment, the hexose cluster comprises at least nine hexose residues with each branch of the configuration having three prongs.

Abstract: Methods are provided for inhibiting stenosis or restenosis following vascular trauma in a mammalian host, comprising administering to the host a therapeutically effective dosage of a cytostatic agent and/or cytoskeletal inhibitor so as to biologically stent the traumatized vessel. Also provided is a method to inhibit or reduce vascular remodeling following vascular trauma, comprising administering an effective amount of a cytoskeletal inhibitor. Further provided are pharmaceutical compositions and kits comprising the therapeutic agents of the invention.

Abstract: Methods for targeting cytotoxins to target sites by administration of a combination of conjugates are provided. Novel cytotoxic combinations for use in such methods are also provided.

Abstract: Radiolabeled annexin and modified annexin conjugates useful for imaging vascular thrombi are described. Methods for making and using such radiolabeled annexin conjugates are also provided.

Abstract: Biotinidase-resistant biotin-DOTA conjugates, and methods of use thereof in diagnostic and therapeutic pretargeting methods are provided. These conjugates are useful in diagnosis and treatment of cancer.

Abstract: Hepatic-directed compounds, reagents useful in making such compounds and associated methods and compositions are discussed. Hepatic-directed compounds are processed by metabolic mechanisms, which generally differ in degree or in kind from the metabolic mechanisms encountered by compounds which are not so directed. Reagents useful in the preparation of hepatic-directed compounds include a hexose cluster characterized by multiple hexose residues connected in an iteratively branched configuration. In one embodiment, the hexose cluster comprises at least four hexose residues with each branch of the configuration having two prongs. In another embodiment, the hexose cluster comprises at least nine hexose residues with each branch of the configuration having three prongs.

Abstract: Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent. Also discussed are mechanisms for in vivo vascular smooth muscle cell proliferation modulation, agents that impact those mechanisms and protocols for the use of those agents.

Abstract: Methods are provided for inhibiting stenosis following vascular trauma or disease in a mammalian host, comprising administering to the host a therapeutically effective dosage of a therapeutic conjugate containing a vascular smooth muscle binding protein that associates in a specific manner with a cell surface of the vascular smooth muscle cell, coupled to a therapeutic agent dosage form that inhibits a cellular activity of the muscle cell. Methods are also provided for the direct and/or targeted delivery of therapeutic agents to vascular smooth muscle cells that cause a dilation and fixation of the vascular lumen by inhibiting smooth muscle cell contraction, thereby constituting a biological stent. Also discussed are mechanisms for in vivo vascular smooth muscle cell proliferation modulation, agents that impact those mechanisms and protocols for the use of those agents.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.

Abstract: Novel clearing agents are provided which comprise biotin analog containing clearance-directing moieties. Preferably such clearance-directing moieties endogenously contain or a rederivatized to expose galactose and/or mannose residues.

Abstract: Novel clearing agents comprising hexose derivatized human serum albumin and ligand molecule(s) are provided. These clearing agents are useful in pretargeting methods to clear previously administered anti-ligand containing conjugates. Preferably, the hexose is mannose or galactose and the ligand and anti-ligand are respectively biotin and avidin or streptavidin.

Abstract: Biotinidase-resistant biotin-DOTA conjugates, and methods of use thereof in diagnostic and therapeutic pretargeting methods are provided. These conjugates are useful in diagnosis and treatment of cancer.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, three-step pretargeting methods are described.

Abstract: Methods for preparing metabolically stable, covalently crosslinked F(ab').sub.2 fragments of antibody molecules for use in labeled form as in vivo diagnostic and therapeutic agents, the stabilized F(ab').sub.2 fragments so produced in free form or conjugated to a chemical moiety, kits containing such fragments, and methods of using these fragments for diagnosis or therapy, are disclosed. In the method, crosslinking is carried out after reduction of inter-heavy chain disulfide bonds, but before cleavage of the crosslinked antibody to produce the F(ab').sub.2 molecules.

Abstract: Conjugates of trichothecenes and agents that bind to a defined population of cells are disclosed. Preferred are conjugates of trichothecene molecules with polyclonal or monoclonal antibodies or fragments thereof that recognize antigens that are present only on tumor cells or are augmented in their expression on tumor cells as compared to normal tissues. Trichothecene molecules are coupled to the agent through non-covalent and covalent linkages, such as peptide bonds, disulfide bonds, thioester bonds, or thioether bonds. A method for inhibiting the growth and metabolism of antigen-positive cells is also disclosed. Derivatized trichothecene compounds prepared for conjugation to targeting agents are also disclosed.

Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described.

Abstract: A fibrin-binding protein such as t-PA is labeled with a detectable substance, such as a radionuclide, and administered to a patient for diagnosis of blood clots and for monitoring the dissolution thereof during therapy. The detectable substance preferably is attached to t-PA through linkers which specifically bind to the portion of the t-PA protein responsible for enzymatic activity, thereby diminishing this activity while leaving the fibrin-binding property of the protein intact.

Abstract: Chelating compounds of specified N.sub.2 S.sub.2 N.sub.3 S derived structure are useful for radiolabeling targeting molecules such as antibodies. Cleavable ester orthioester linkers connect the radionuclide metal chelates to the antibodies. The radiolabeled antibodies have improved biodistribution properties, including reduced localization within the intestines and kidneys.

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.