Cholecystokinin B receptor targeting for imaging and therapy
Conjugates are described herein where CCK2R targeting ligands are attached to an active moiety, such as therapeutic agent or an imaging agent, through a linker. The conjugates can be used in the detection, diagnosis, imaging and treatment of cancer.
1. A conjugate of the formula:
B-L-D
wherein
B is a targeting ligand of Formula I
L is a bivalent or polyvalent linker; and
D is a fluorescein or fluorescein isothiocyanate (FITC) optical imaging agent;
or a pharmaceutically acceptable salt thereof.
2. The conjugate of claim 1 , wherein L is a non-releasable linker.
3. The conjugate of claim 1 , wherein L comprises one or more amino acids.
4. The conjugate of claim 1 , wherein L comprises glutamic acid.
5. The conjugate of claim 1 , wherein L comprises a carbamate moiety.
6. The conjugate of claim 1 , wherein L comprises a polyethylene glycol (PEG)n, and n is an integer 0 to 6.
7. The conjugate of claim 1 , wherein L is
HN-Glu-Arg-Asp-CO (L1),
HN-Glu-PS-Glu-PS-CO (L2), or
HN-Octanoyl-Glu-PS-Glu-PS-CO (L3), and
PS is of formula
8. A pharmaceutical composition comprising a conjugate of claim 1 and a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 , wherein L is a non-releasable linker.
10. The pharmaceutical composition of claim 8 , wherein L comprises one or more amino acids.
11. The pharmaceutical composition of claim 8 , wherein L comprises glutamic acid.
12. The pharmaceutical composition of claim 8 , wherein L comprises a carbamate moiety.
13. The pharmaceutical composition of claim 8 , wherein L comprises a polyethylene glycol (PEG)n, and n is an integer 0 to 6.
14. The pharmaceutical composition of claim 8 , wherein L is HN-Glu-Arg-Asp-CO (L1), HN-Glu-PS-Glu-PS-CO (L2), or HN-Octanoyl-PS-Glu-PS-CO (L3), and PS is of formula