Anti-met therapy for previously diagnosed cancer patients
AssigneeGe Healthcare Limited
InventorsGrethe Tang Dalsgaard, Ian Andrew Wilson
Life of this patent
Estimating the term…
Abstract
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.
Claims13
A method of assisting in determining whether or not a patient previously diagnosed with cancer, is susceptible to anti-Met therapy, said method comprising:
- (i) administering an imaging agent which comprises an 18F-radiolabelled c-Met binding cyclic peptide to said patient;
- (ii) using positron emission tomography (PET) imaging at least one site of said cancer of said patient with the imaging agent of step (i);
- (iii) determining from the imaging of step (ii) whether or not there is elevated uptake of said imaging agent at said site;
- (iv) when step (iii) shows elevated uptake, said patient is susceptible to said anti-Met therapy;
- (v) when step (iii) shows no elevated uptake, said patient is not susceptible to said anti-Met therapy;
- 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), (SEQ-2), or (SEQ-3):
- wherein SEQ-1 is -Cysa-X1-Cysc-X2-Gly-Pro-Pro-X3-Phe-Glu-Cysd-Trp-Cysb-Tyr-X4-X5-X6-;
- wherein SEQ-2 is Ser-Cysa-X1-Cysc-X2-Gly-Pro-Pro-X3-Phe-Glu-Cysd-Trp-Cysb-Tyr-X4- X5-X6;
- wherein SEQ-3 is Ala-Gly-Ser-Cysa-X1-Cysc-X2-Gly-Pro-Pro-X3-Phe-Glu-Cysd-Trp-Cysb-Tyr-X4-X5-X6-Gly-Thr;
- 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 wherein 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,
- wherein [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 MIG comprises at least one of N-acylated groups —NH(C═O)RG, carboxamide, tert-butyl ester, benzyl ester, cyclohexyl ester, amino alcohol or a polyethyleneglycol (PEG) building block;
- wherein the acyl group —(C═O)RG has RG selected from the group consisting of C1-6 alkyl, C3-10 aryl groups and comprises a polyethyleneglycol (PEG) building block;
- wherein cMBP is labelled at the Lys residue of the A or A′ groups with 18F.
Dependencies are inferred from the claim text.