The invention provides compositions, kits and methods to treat a hyperproliferative disorder with an agent that increases expression of MCR1 and an MCR1 ligand. The invention also provides a method of treating drug-resistant melanoma, comprising administering an MCR1 ligand to a patient in need thereof. The present invention also provides in certain embodiments a melanoma-targeting conjugate comprising Formula I:
T-L-X
wherein T is a MCR1 ligand, L is a linker, and X an anti-cancer composition, for the therapeutic treatment of a hyperproliferative disorder. The present invention also provides methods, kits and uses of the conjugate of Formula I.

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.

Provided herein, inter alia, are methods and compositions for detection of vascular calcification.

Metal complexes including a radionuclide and a compound of Formula I and Formula II are potent inhibitors of PSMA. ##STR00001##

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.

The present disclosure relates to prostate specific membrane antigen (PSMA) ligands. In particular, the disclosure relates to PSMA ligands having a glutamate-urea-lysine (GUL) moiety and a chelating agent that can comprise a radiometal. The disclosure also relates to the use of these compounds in imaging and in the treatment of prostate cancer.

A compound for measurement of thiopurine pathway directed systems imaging and therapy including a chelator and a thiopurine ligand is provided. A method of synthesizing the compound is also provided, and the compound may be further prepared in pharmaceutical formulations or kits for therapy or molecular imaging.

A PSMA-specific agent comprising a compound according to Formula I or Formula II: wherein S.sub.1 is absent or is an organic spacer group comprising 3-10 carbons; A is an amino acid chain comprising 1 to 5 amino acids wherein at least one of the amino acids is selected from glutamic acid and aspartic acid; S2 is absent or is an organic spacer group comprising 1 to 15 carbons and/or 0 to 2 amino acids; I.sub.1 is an imaging group; and I.sub.2 is absent or is an imaging group. The PSMA-specific agents can be used to image PSMA within a tissue region and/or for the treatment of a cancer, such as prostate cancer.

##STR00001##

This disclosure provides a family of compounds that absorb and fluoresce in the short wave infrared region (SWIR, optionally 1000 nm to 1300 nm), including hydrophilic compounds that exhibit absorption and emission spectral profiles in aqueous solutions substantially similar to those observed in organic solvents such as methanol or DMSO. The compounds can be chemically linked to biomolecules including proteins, nucleic acids, and therapeutic small molecules. The compounds are useful for imaging in a variety of medical, biological and diagnostic applications, including SWIR in vivo imaging of regions of interest within a mammal.

Fibroblast activation protein (FAP)-targeting compounds (e.g., conjugates); a method for imaging cancer or fibrosis; and methods for treating an inflammatory disease/disorder and cancer.