The present invention relates to compounds (reactive conjugates) for the chemical modification of therapeutic antibodies or proteins. The compounds enable the regioselective attachment of a payload to an antibody or antibody fragment in one single step, thereby producing a modified antibody or modified antibody fragment, which can be used for diagnosing, monitoring, imaging or treating disease.

The present invention provides antibodies and related molecules that bind to chemokine receptor 4 (CXCR4). The invention further provides antibody-drug conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and anti-CXCR4 antibody-drug conjugates for the treatment of a disorder associated with CXCR4 function or expression (e.g., cancer), such as colon, RCC, esophageal, gastric, head and neck, lung, ovarian, pancreatic cancer or hematological cancers.

The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.

The invention relates to novel biocompatible hybrid nanoparticles of very small size, useful in particular for diagnostics and/or therapy.

The purpose of the invention is to offer novel nanoparticles which are useful in particular as contrast agents in imaging (e.g. MRI) and/or in other diagnostic techniques and/or as therapeutic agents, which give better performance than the known nanoparticles of the same type and which combine both a small size (for example less than 20 nm) and a high loading with metals (e.g. rare earths), in particular so as to have, in imaging (e.g. MRI), strong intensification and a correct response (increased relaxivity) at high frequencies. The method for the production of these nanoparticles and the applications thereof in imaging and in therapy also form part of the invention.

Disclosed are multimeric compounds of K1 domains from the Hepatocyte Growth Factor/Scatter Factor (HGF/SF) being able to induce activation of the tyrosine kinase receptor MET and their uses.

The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the focus is notably on a subpopulation of stromal cells, known as cancer-associated fibroblasts, which are present in more than 90% of epithelial carcinomas, including pancreatic, colon, and breast cancer. Cancer-associated fibroblasts feature high expression of FAP, which is not detectable in adult normal tissue but is associated with a poor prognosis in cancer patients. The present invention provides small-molecule radiopharmaceutical and imaging agents based on a FAP-specific inhibitor.

Antibodies that include a sulfatase motif-containing tag in a constant region of an immunoglobulin (Ig) heavy chain polypeptide are disclosed. The sulfatase motif can be converted by a formylglycine-generating enzyme (FGE) to produce a formylglycine (fGly)-modified Ig heavy chain polypeptide. An fGly-modified Ig heavy chain polypeptide of the antibody can be covalently and site-specifically bound to a moiety of interest to provide an antibody conjugate. The disclosure also encompasses methods of production of such tagged Ig heavy chain polypeptides, fGly-modified Ig heavy chain polypeptides, and antibody conjugates, as well as methods of use of same.

Provided herein are imaging agents, antidotes to the imaging agents and methods of using the same to image a thrombus or blood clot or thrombin including sites of thrombin accumulation and to diagnose and treat thrombosis. The imaging agents include an aptamer capable of binding the thrombus or thrombin in particular linked to a reporter moiety. The imaging agents may be used to label the thrombus or sites of thrombin accumulation. Antidotes capable of binding to the aptamer in the imaging agent are also provided. The antidotes may further be linked to a quencher capable of quenching the reporter moiety.

The present invention relates to a compound or a pharmaceutically acceptable salt thereof having a chemical structure comprising: A compound or a pharmaceutically acceptable salt thereof of formula (I): (A)-x.sub.1-(B)-x.sub.2-(C), wherein (A) is at least one motif specifically binding to cell membranes of neoplastic cells; (B) at least one chelator moiety of radiometals; (C) a dye moiety; x.sub.1 is a spacer covalently connecting (A) and (B); x.sub.2 is a spacer or a chemical single bond connecting (B) and (C); wherein (C) has the formula

##STR00001##

wherein R.sup.1 to R.sup.4, R.sup.9, a, b, Y and X.sup.1 to X.sup.4 have the meaning as indicated in the claims and description. The invention further relates to compositions comprising said compounds as well as a method for detecting neoplastic cells in a sample in vitro with the aid of the compounds or composition.

Described herein are nanoprobes comprising ultrasmall aminated and cRGDY-conjugated nanoparticles labeled with Zirconium-89 (.sup.89Zr) and methods of their use. The provided compositions are renally clearable and possess suitable blood circulation half-time, high tumor active targeting capability, dominant renal clearance, low liver accumulation, and a high tumor-to-background ratio. The described nanoprobes exhibit great potential as “target-or-clear” tracers to human subjects for systemic targeted imaging (or treatment) of cancer.