PSMA-targeted NIR dyes and their uses

A method of optical imaging of a biological tissue that expresses PSMA, the method comprising:

• (a) contacting the biological tissue with a composition a compound having the structural formula:
• or a pharmaceutically acceptable salt thereof, or isotopes thereof, wherein:
• R1 represents a hydrogen or SO3H;
• R2 represents a hydrogen, or CH3, or C3H6SO3−, or C3H6SO3H or C4H8SO3−, or C4H8SO3H or C3H6N+(CH3)3;
• R3, and R5 each represents a carbon, optionally one or more sharing bonds, or oxygen, or sulfur, or nitrogen
• R4 represents a carbon with optionally one or more sharing bonds;
• R6 represents nitrogen, oxygen, or sulfur or no atom (direct C—C bond between aromatic ring and vinyl ring);
• R7 is optional and when present represents electron donating aromatic substitution group;
• R8 is optional and when present represents linkers with aromatic amino acids such as Phe, Trp, His, Tyr, or derivative of them, and/or cationic amino acids such Arg, Lys, or derivative of them, and/or anionic amino acids such as Asp, Glu or derivative of them, and/or unnatural amino acids of aromatic/cationic/anionic acids or derivative;
• R9 represents a PEG, N-amino-dPEG2-acid, PEA, or derivative of them;
• R10 represents a CO2H, PO3H2, SO3H, CH2SO3H, CH2CONHCH2SO3H, CH2CONHCH2CH2SO3H;
• R11 represents CO2H, SO3H, CH2CONHCH2SO3H, CH2CONHCH2CH2SO3H;
• and
• R12 represents independently represents a hydrogen, a methyl group, CH2COOH, a CH2 and may optionally represent each a CH2 sharing a bond,
• (b) allowing time for the compound in the composition to distribute within the biological target;
• (c) illuminating the tissue with an excitation light of a wavelength absorbable by the compound;
• and
• (d) detecting the optical signal emitted by the compound.

A method of identifying a target cell type in a biological sample comprising:

• a) contacting the biological sample with a compound having the formula:
• B—X—Y—Z, wherein
• B comprises a compound capable of binding to prostate specific membrane antigen (PSMA),
• X, is selected from the group consisting of polyethylene glycol (PEG), N-amino-dPEG2-acid and polyethylene amine (PEA),
• Y comprises at least one amino acid, or derivative thereof, and
• Z comprises a near-infra red (NIR) dye,
• b) for a time and under conditions that allow for binding of the compound to at least one cell of the target cell type or vasculature of the target tissue;
• and
• c) optically detecting the presence or absence of the compound of in the biological sample, wherein presence of the compound in detecting step b) indicates that the target cell type is present in the biological sample.