The present technology provides compounds as well as compositions including such compounds useful in targeted radiotherapy of cancer and/or mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”) where the compounds are represented by the following:

##STR00001##

or a pharmaceutical y acceptable salt thereof,

##STR00002##

or a pharmaceutically acceptable salt thereof,

##STR00003##

or a pharmaceutically acceptable salt thereof,
wherein M.sup.1 is independently at each occurrence an alpha-emitting radionuclide. Equivalents of such compounds are also disclosed.

Provided are compositions and methods for treating cancers and precancerous proliferative disorders in a mammalian subject that involve the combination use of a radiotherapeutic agent, such as a radiolabeled CD33, DR5, 5T4, HER2, HER3, or TROP2 targeting agent, and a CD47 checkpoint inhibitor, such as a SIRPα-IgG Fc fusion protein or a monoclonal antibody against CD47 or SIRPα.

Provided are compositions and methods for treating cancers and precancerous proliferative disorders in a mammalian subject that involve the combination use of a radiotherapeutic agent, such as a radiolabeled CD33, DR5, 5T4, HER2, HER3, or TROP2 targeting agent, and a CD47 checkpoint inhibitor, such as a SIRPα-IgG Fc fusion protein or a monoclonal antibody against CD47 or SIRPα.

The present technology provides compounds as well as compositions including such compounds useful in targeted radiotherapy of cancer and/or mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”) where the compounds are represented by the following:

##STR00001## or a pharmaceutically acceptable salt thereof,

##STR00002## or a pharmaceutically acceptable salt thereof,

##STR00003## or a pharmaceutically acceptable salt thereof,
wherein M.sup.1 is independently at each occurrence an alpha-emitting radionuclide. Equivalents of such compounds are also disclosed.

The present technology provides compounds as well as compositions including such compounds useful in targeted radiotherapy of cancer and/or mammalian tissue overexpressing prostate specific membrane antigen (“PSMA”) where the compounds are represented by the following: ##STR00001## or a pharmaceutically acceptable salt thereof, ##STR00002## or a pharmaceutically acceptable salt thereof, ##STR00003## or a pharmaceutically acceptable salt thereof,
wherein M.sup.1 is independently at each occurrence an alpha-emitting radionuclide. Equivalents of such compounds are also disclosed.

Provided herein are methods, kits, and compositions for stratifying and treating subjects, e.g., subjects having cancer. In some examples, the methods involve use of a radiolabelled heavy chain variable domain derived from a heavy chain antibody (V.sub.HH), or a functional fragment thereof, as both a screening agent and a treatment agent. In some examples, the V.sub.HH, or a functional fragment thereof, that is radiolabelled with a radioisotope that is both a γ-emitter and β-emitter.

Provided herein are diabodies that comprise extension sequences and antigen binding constructs that comprise extension sequences.

This invention provides a method for treating a subject afflicted with cancer, comprising administering to the subject (i) a PARP inhibitor in conjunction with (ii) a radioisotope-labeled agent that targets cancer cells in the subject, wherein the amounts of the PARP inhibitor and labeled agent, when administered in conjunction with one another, are therapeutically effective. This invention also provides a method for inducing the death of a cancer cell, comprising contacting the cell with (i) a PARP inhibitor in conjunction with (ii) a radioisotope-labeled agent that targets the cancer cell, wherein the amounts of PARP inhibitor and labeled agent, when concurrently contacted with the cell, are effective to induce the cell's death.

The invention provides a method for the formation of a tissue-targeting thorium complex, said method comprising: a) forming an octadentate chelator comprising four hydroxypyridinone (HOPO) moieties, substituted in the N-position with a C.sub.1-C.sub.3alkyl group, and a coupling moiety terminating in a carboxylic acid group; b) coupling said octadentate chelator to at least one tissue-targeting peptide or protein comprising at least one amine moiety by means of at least one amide-coupling reagent whereby to generate a tissue-targeting chelator; and c) contacting said tissue-targeting chelator with an aqueous solution comprising an ion of at least one alpha-emitting thorium isotope. A method of treatment of a neoplastic or hyperplastic disease comprising administration of such a tissue-targeting thorium complex, as well as the complex and corresponding pharmaceutical formulations are also provided.

The invention discussed in this application relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours.