Patent ID: 8431111

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): 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 ; 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; wherein when M IG is at the amino terminus, it is selected from 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; wherein when M IG is at the carboxy terminus, it is selected from 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; Bzp M is a benzopyrylium dye of Formula II: where: Y 1 is a group of Formula Y a or Y b R 1 -R 4 and R 9 -R 13 are independently selected from H, —SO 3 M 1 , Hal, R a or C 3-12 aryl, where each M 1 is independently H or Bc; R 5 is H, C 1-4 alkyl, C 3-12 arylsulfonyl, Cl, or R 5 together with one of R 6 , R 14 , R 15 or R 16 may optionally form a 5- or 6-membered unsaturated aliphatic, unsaturated heteroaliphatic or aromatic ring; R 6 and R 16 are independently R a groups; R 7 and R 8 are independently C 1-4 alkyl, C 1-4 sulfoalkyl or C 1-6 hydroxyalkyl or optionally together with one or both of R 9 and/or R 10 may form a 5- or 6-membered N-containing heterocyclic or heteroaryl ring; X is —CR 14 R 15 —, —O—, —S—, —Se—, —NR 16 — or —CH═CH—, where R 14 to R 16 are independently R a groups; R a is C 1-4 alkyl, C 1-4 sulfoalkyl, C 1-6 carboxyalkyl or C 1-6 hydroxyalkyl; w is 1 or 2; J is a biocompatible anion; with the proviso that Bzp M comprises at least one sulfonic acid substituent chosen from the R 1 to R 16 groups.