Conjugates of topoisomerase I inhibitors linked to a macromolecule through a linkage that undergo beta elimination in situ in combination with one or more of an assessed defect in DNA damage response (DDR) in a subject bearing cancer, a cell cycle checkpoint inhibitor and/or a DDR inhibitor provides improved outcomes for cancer-bearing subjects.

The present disclosure provides compositions and methods for the detection and treatment of cancer. Specifically, the compositions of the present technology include novel compounds that may be complexed with a radioisotope. Also disclosed herein are methods of the using the DOTA-haptens of the present technology in diagnostic imaging as well as pretargeted radioimmunotherapy.

Disclosed is a method for increased target specificity of a mannosylated carbohydrate polymeric therapeutic and/or diagnostic compound by administering a blocking composition comprising a backbone and one or more C-type lectin receptor targeting moieties attached thereto with an effective amount of the mannosylated dextran therapeutic and/or diagnostic compound. The administration of the blocking compound results in higher localization of the mannosylated dextran therapeutic and/or diagnostic compounds to a desired target other than the liver and/or spleen compared to without the administration of the blocking compound. The molecular weight of the blocking composition backbone is between about 1 kDa and about 35 kDa.

A method of diagnosing a CD206 expressing cell-related disorder by administering a pharmaceutical composition to a subject, the composition including a carrier molecule having a detectable moiety attached thereto. The carrier molecule has a dextran backbone, and at least one receptor substrate conjugated, directly or indirectly, to the dextran backbone, wherein the receptor substrate is chosen so as to specifically bind to CD206. A method of treating a CD206 expressing cell-related disorder is also provided, as well as an ex vivo method and kit for quantitating the number of cells expressing CD206 in a bodily fluid.

Disclosed herein is method for conjugating a metal chelating agent to a functionalized dextran by reacting a chelator with an aminated dextran backbone, where the chelator comprises a one, and only one, derivatized carboxylic acid group to form a chelator-dextran complex. In certain aspects, the dextran-chelator complex is substantially free of intra- or intermolecular crosslinking. In certain aspects, the functionalized dextran is an amine dextran, an alkynyl dextran, or a thiol dextran. In exemplary implementations, the functionalized dextran is an amine dextran. In further embodiments, one and only one carboxylic acid group on the chelating agent is derivatized as a N-hydroxysuccinimide (NHS) ester.

Compositions and methods of using these compositions that can include a targeting moiety and a therapeutic agent are described herein. These compositions can be used for diagnosing and/or treating flaviviridae-family viruses including Zika virus, dengue virus, and yellow fever.

A method of diagnosing an inflammasome-mediated disorder includes administering a pharmaceutical composition to a subject. The composition includes a carrier molecule having a detectable moiety attached thereto. The carrier molecule includes a non-toxic carbohydrate-based backbone. The method also includes after the administering step, detecting a presence of the detectable moiety at a predetermined location in the subject.

Advantage is taken of the enhanced permeability and retention effect (EPR effect) to shield normal tissue from exposure to combinations of chemotherapeutic agents. Imaging agents that exhibit the enhanced permeability and retention (EPR) effect in solid tumors are useful in mimicking the behavior of chemotherapeutic or other drugs for treatment of said tumor conjugated to carriers of similar size and shape to the carriers of said imaging agents.

Provided herein is a dendrimer comprising: i) a core unit (C); and ii) building units (BU), wherein the core unit is covalently attached to at least two building units; the dendrimer having from two to six generations of building units; wherein building units of different generations are covalently attached to one another; and the dendrimer further comprising: iii) one or more first terminal groups attached to an outermost building unit, wherein each first terminal group comprises a radionuclide-containing moiety; and iv) one or more second terminal groups attached to an outermost building unit, wherein each second terminal group comprises a pharmacokinetic-modifying moiety; or a salt thereof. Also provided are compositions comprising the dendrimers, and methods of using the dendrimers and compositions in diagnostic and therapeutic applications.

The present invention provides extracorporeal removal of targeting vectors applied in pretargeted therapy and diagnostics in animals and humans. The method and the means for extracorporeal removal of the targeting vectors is based on binding agents with inverse electron demand Diels-Alder (IEDDA) cycloaddition reactivity. The targeting vector comprises a therapeutic agent, a diagnostic agent or a theranostic agent and a chemical entity with IEDDA reactivity whereas the extracorporeal means comprises a column with a biocompatible solid support to which a chemical entity with complementary IEDDA reactivity is attached.