NOVEL RADIOLABELLED CXCR4-TARGETING COMPOUNDS FOR DIAGNOSIS AND THERAPY

摘要

This application relates to compounds of Formula (I): [targeting peptide]-N(R¹)-X¹(R²)L¹-[linker]-R^X_n1 (I). The targeting peptide is cyclo[L-Phe-L-Tyr-L-Lys(iPr)-D-Arg-L-2-Nal-Gly-D-Glu]-L-Lys(iPr). R¹ is H or methyl. X¹ is an optionally substituted C₁-C₁₅ hydrocarbon optionally comprising heteroatoms. R² is C(O)OH or C(O)NH₂. L¹ is a linkage (thiolether, amide, maleimide-thiol, triazole). The linker has a net negative charge at physiological pH and is a linear or branched chain of 1-10 units of X²L² and/or X²(L²)_2, wherein: each X² is, independently, an optionally substituted C₁-C₁₅ hydrocarbon optionally comprising heteroatoms; and each L² is a linkage. The linker optionally further comprises an albumin binder bonded to an L². Each R^X is a radiolabelling group linked through a separate L², selected from: a metal chelator; a prosthetic group containing trifluoroborate (BF₃); or a prosthetic group containing a silicon-fluorine-acceptor moiety. The compounds may be useful for imaging CXCR4-expressing tissues or for treating CXCR4-associated diseases or conditions (e.g. cancer).