| 主权项 |
1. An imaging agent which comprises a radioactive xTc complex of a chelator conjugate of a c-Met binding peptide, said chelator conjugate being of Formula I:
Z1-[cMBP]-Z2 (I) where:xTc is the radioisotope 94mTc or 99mTc;cMBP is an 18 to 30-mer c-Met binding cyclic peptide of Formula II:
-(A)x-Q-(A′)y- (II) where Q is the amino acid sequence (SEQ-1): -Cysa-X1-Cysc-X2-Gly-Pro-Pro-X3-Phe-Glu-Cysd-Trp-Cysb-Tyr-X4-X5-X6- wherein X1 is Asn, His or Tyr; X2 is Gly, Ser, Thr or Asn; X3 is Thr or Arg; X4 is Ala, Asp, Glu, Gly or Ser; X5 is Ser or Thr; X6 is Asp or Glu; and Cysa-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; one of A and A′ is any amino acid other than Cys, and the other one of A or A′ is a linker peptide selected from: -Gly-Gly-Gly-Lys- (SEQ-4), -Gly-Ser-Gly-Lys- (SEQ-5) or -Gly-Ser-Gly-Ser-Lys- (SEQ-6) wherein a Z3 group is attached to the epsilon amine group of the Lys residue of said linker peptide and Z3 is conjugated to xTc; x and y are independently integers of value 0 to 13, and are selected such that [x+y]=1 to 13; Z1 is attached to the N-terminus of cMBP, and is —NH(C═O)RG where —(C═O)RG has RG selected from: C1-6alkyl, or C3-10 aryl groups or comprises a polyethyleneglycol (PEG) building block; Z2 is attached to the C-terminus of cMBP and is a primary amide; Z3 is a chelator of Formula (III): wherein E1-E6 are each independently an R′ group; each R′ is independently H or C1-4 alkyl, C3-7 alkylaryl, C2-7 alkoxyalkyl, C1-4 hydroxyalkyl, C1-4 fluoroalkyl, C2-7 carboxyalkyl or C1-4 aminoalkyl, or two or more R′ groups together with the atoms to which they are attached form a carbocyclic, heterocyclic, saturated or unsaturated ring; L is a synthetic linker group of formula -(A″)m- wherein each A″ is independently —CR2-, —CR═CR—, —C═C—, —CR2CO2—, —CO2CR2—, —NRCO—, —CONR—, —NR(C═O)NR—, —NR(C═S)NR—, —SO2NR—, —NRSO2—, —CR2OCR2-, —CR2SCR2—, —CR2NRCR2—, a C4-8 cycloheteroalkylene group, a C4-8 cycloalkylene group, a C5-12 arylene group, or a C3-12 heteroarylene group, or a monodisperse polyethyleneglycol (PEG) building block; each R is independently selected from H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxyalkyl or C1-4 hydroxyalkyl; and m is an integer of value 1 to 10. |
