Patent ID: 8529874

Claim:
An imaging agent which comprises a conjugate of Formula I: where: Z 1 is attached to the N-terminus of cMBP, and is H or M IG ; Z 2 is attached to the C-terminus of cMBP and is OH, OB c , or M IG , where B c is a biocompatible cation; cMBP is a cMet binding cyclic peptide of 17 to 30 amino acids which comprises the amino acid sequence (SEQ-1), (SEQ-2) or (SEQ-3): SEQ-1 Cys a -X 1 -Cys c -X 2 -Gly-Pro-Pro-X 3 -Phe-Glu-Cys d -Trp-Cys b -Tyr-X 4 -X 5 -X 6 ; SEQ-2: Ser-Cys a -X 1 -Cys c -X 2 -Gly-Pro-Pro-X 3 -Phe-Glu-Cys d -Trp-Cys b -Tyr-X 4 -X 5 -X 6 ; SEQ-3: Ala-Gly-Ser-Cys a -X 1 -Cys c -X 2 -Gly-Pro-Pro-X 3 -Phe-Glu-Cys d Trp-Cys b Tyr-X 4 -X 5 -X 6 -Gly-Thr; wherein X 1 is Asn, His or Tyr; X 2 is Gly, Ser, Thr or Asn; X 3 is Thr or Arg; X 4 is Ala, Asp, Glu, Gly or Ser; X 5 is Ser or Thr; X 6 is Asp or Glu; and Cys a-d are each cysteine residues such that residues a and b as well as c and d are cyclised to form two separate disulfide bonds; M IG is a metabolism inhibiting group which is a biocompatible group which inhibits or suppresses in vivo metabolism of the peptide; and is chosen from: for the peptide amine terminus: N-acylated groups —NH(C═O)R G where the acyl group —(C═O)R G has R G chosen from: C 1-6 alkyl, C 3-10 aryl groups or comprises a polyethyleneglycol (PEG) building block; for the peptide carboxyl terminus: carboxamide, tert-butyl ester, benzyl ester, cyclohexyl ester, amino alcohol or a polyethyleneglycol (PEG) building block; L is a synthetic linker group of formula -(A) m - wherein each A is independently —CR 2 —, —CR═CR—, —C≡C—, —CR 2 CO 2 —, —CO 2 CR 2 —, —NRCO—, —CONR—, —NR(C═O)NR—, —NR(C═S)NR—, —SO 2 NR—, —NRSO 2 —, —CR 2 OCR 2 —, —CR 2 SCR 2 —, —CR 2 NRCR 2 —, a C 4-8 cycloheteroalkylene group, a C 4-8 cycloalkylene group, a C 5-12 arylene group, or a C 3-12 heteroarylene group, an amino acid, a sugar or a monodisperse polyethyleneglycol (PEG) building block; each R is independently chosen from H, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxyalkyl or C 1-4 hydroxyalkyl; m is an integer of value 1 to 20; n is an integer of value 0 or 1; IM is an optical reporter imaging moiety suitable for imaging the mammalian body in vivo using light of green to near-infrared wavelength 600-1200 nm, which is a cyanine dye of Formula III: where: R 1 and R 2 are independently H or SO 3 M 1 , and at least one of R 1 and R 2 is SO 3 M 1 , where M 1 is H or B c , where B C is a biocompatible cation; R 3 and R 4 are independently C 1-4 alkyl or C 1-6 carboxyalkyl; R 5 , R 6 , R 7 and R 8 are independently R a groups; wherein R a is C 1-4 alkyl, C 1-6 carboxyalkyl or —(CH 2 ) k SO 3 M 1 , where k is an integer of value 3 or 4; with the proviso that the cyanine dye has a total of 1 to 4 SO 3 M 1 substituents in the R 1 , R 2 and R a groups.