An antibody or antigen-binding portion thereof which binds to PSMA and comprises a heavy chain variable domain comprising the sequence given in SEQ ID NO:33, wherein SEQ ID NO:33 is: EVQLVQSGX.sup.9E X.sup.11KKPGASVKV SCKX.sup.24SGYTFT EYTIHWVX.sup.38QA X.sup.41 GKGLEWIGN INPNX.sup.55GGTTY NOKFEDRX.sup.68TX.sup.70 TVDKSTSTAY MELSSLRSED TAVYYCAAGW NFDYWGOGTT VTVSS wherein: X.sup.9 is A or P X.sup.11 is V or L X.sup.24 is A or T X.sup.38 is R or K X.sup.41 is P or H X.sup.55 is N or Q X.sup.68 is V or A; and X.sup.70 is I or L whereby the heavy chain variable domain comprises up to 3 amino acid sequence modification(s) between positions 1-30, 36-49, 67-98 and 105-115 of SEQ ID NO: 33. The invention also provides compounds that include the antibody or antigen-binding portion thereof, such as conjugates, and their use in the treatment or diagnosis of diseases, in particular cancers, particularly prostate cancer.

Compounds having formula I,

##STR00001##

or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.

Provided herein are compositions, systems, and methods for minimally-invasive assessment of toxicity-induced tissue injury. In particular, external (e.g., whole-body) scanning is employed to detect toxicity-induced injuries, such as those caused by chemotherapeutics.

A method for preparing .sup.18F radiolabeled biomolecules and agents for .sup.18F-PET imaging is disclosed herein. A perfluoroaryl-conjugated target tracer is synthesized and purified with temperature and solvent conditions that are mild for the tracer molecule. The purified perfluoroaryl-conjugated target tracer is then labeled with .sup.18F using .sup.18F salts within a short reaction time, and with temperature and solvent conditions that are mild for the tracer molecule. The method provides a quick and convenient process that maintains the biological activities of the target molecules. The radio-labeled biomolecules may be used as contrast agents for Positron Emission Tomography (PET).

Disclosed are compounds, compositions, and methods involving cyclic peptides that can bind to KRAS (G12D) oncogenic protein. For example, disclosed are cyclic peptides that selectively bind KRAS (G12D) oncogenic protein. Also disclosed are methods of inhibiting KRAS (G12D) oncogenic protein in a cancer cell expressing KRAS (G12D) oncogenic protein. In some forms, the method comprises incubating the cancer cell with any one or more of the disclosed cyclic peptides. In some forms, the method comprises bringing into contact the cancer cell with any one or more of the disclosed cyclic peptides.

Described herein are novel conjugates containing an inhibitor (e.g., a PSMA inhibitor, e.g., a gastrin-releasing peptide receptor inhibitor) and metal chelator that are covalently attached to a macromolecule (e.g., a nanoparticle, a polymer, a protein). Such conjugates exhibit distinct properties over the free, unbound inhibitor/chelator construct.

Described herein are high-boiling-point-based nanoparticles that release drugs specifically at the focus of ultrasound. The specific conjunction of the high-boiling-point-based nanoparticle formulation with low-frequency ultrasound can be used to deliver therapeutics in a safe and effective manner. The effectiveness and safety of the release is validated in vitro and in non-human primates.

The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo. In order to target a specific cell type, the nanoparticle may further be conjugated to a ligand, which is capable of binding to a cellular component associated with the specific cell type, such as a tumor marker. In one embodiment, a therapeutic agent may be attached to the nanoparticle. To permit the nanoparticle to be detectable by not only optical fluorescence imaging, but also other imaging techniques, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), computerized tomography (CT), bioluminescence imaging, and magnetic resonance imaging (MRI), radionuclides/radiometals or paramagnetic ions may be conjugated to the nanoparticle.

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.

The present invention provides a compound of Formula (I) as defined herein. The present invention also provides a nanoparticle comprising a plurality of the conjugates of the present invention, and methods of using the nanoparticles for drug delivery, treating a disease, and methods of imaging.