METHOD FOR PATIENT SELECTION

摘要

The present invention relates to methods useful in the selection of cancer patients suitable for treatment with therapies directed at c-Met. The method employs imaging agents which comprise 18F-radiolabelled c-Met binding peptides suitable for positron emission tomography (PET) imaging in vivo. Also disclosed are methods of treatment, methods of monitoring therapy directed atc-Met and the use of the imaging agents and peptides in the methods of the invention.

主权项

1. A method to assist in the determination of whether an individual patient previously diagnosed with cancer, is susceptible to treatment with anti-Met therapy, said method comprising:
(i) provision of an imaging agent which comprises an 18F-radiolabelled c-Met binding cyclic peptide; (ii) imaging at least one site of said cancer with the imaging agent of step (i), wherein said imaging agent had been previously administered to said patient; (iii) making a determination from the imaging of step (ii) whether or not there is elevated uptake of said imaging agent at said site; (iv) when the determination of step (iii) shows elevated uptake, the cancer is deemed to overexpress c-Met, and anti-Met therapy is determined to be suitable for said patient; (v) when the determination from step (iii) shows no elevated uptake, the cancer is deemed not to overexpress c-Met, and anti-Met therapy is determined not to be suitable for said patient; wherein said c-Met binding cyclic peptide is an 18 to 30-mer cyclic peptide of Formula I:
Z1-[cMBP]-Z2  (I) where: cMBP is 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;A and A′ are independently any amino acid other than Cys, with the proviso that at least one of A and A′ is present and is Lys;x and y are independently integers of value 0 to 13, and are chosen such that [x+y]=1 to 13; Z1 is attached to the N-terminus of cMBP, and is H or MIG; Z2 is attached to the C-terminus of cMBP and is OH, OBc, or MIG,
where Bc is a biocompatible cation;each MIG is independently a metabolism inhibiting group which is a biocompatible group which inhibits or suppresses in vivo metabolism of the cMBP peptide; wherein cMBP is labelled at the Lys residue of the A or A′ groups with 18F.