Cholecystokinin 2 receptor targeted NIR imaging and use thereof
Compounds are described herein where CCK2R targeting ligands are attached to an imaging agent through a linker. The compounds can be used in the detection, diagnosis, imaging and treatment of cancer.
1. A compound having the formula B-L-Z
wherein B is a targeting ligand capable of selectively binding to CCK2R and/or CCK2i4svR selected from the group consisting of
wherein the values of m and n are independently selected from the values 0, 1, or 2,
wherein L is a linker selected from the group consisting of glutamic acid,
and
wherein Z is an imaging agent represented by the formula:
wherein, R 1 is independently selected from the group consisting of O, S, N and C, R 2 is independently selected from the group consisting of CH 2 and CH 2 CH 2 , and each of R 3 , R 4 , and R 5 are independently selected from the group consisting of H, Na, K, and NH 4 or a salt thereof, or isotopes thereof wherein L enhances the binding affinity and biodistribution of the compound.
2. The compound of claim 1 wherein Z has an absorption and emission maxima in the visible spectrum.
3. The compound of claim 1 wherein Z has an absorption and emission maxima of about 680 nm to about 800 nm.
4. The compound of claim 1 , wherein the compound is capable of or adapted to fluoresce after distribution thereof in tissue.
5. The compound of claim 1 wherein the compound is adapted to fluoresce by subjecting the compound to excitation light of near infrared wavelength.
6. The compound of claim 1 wherein the compound is highly selective for targeting to a tumor cell.
7. A compound having the formula selected from the group consisting of
wherein, R 1 is independently selected from the group consisting of O, S, N and C, R 2 is independently selected from the group consisting of CH 2 and CH 2 CH 2 , and each of R 3 , R 4 , and R 5 are independently selected from the group consisting of H, Na, K, and NH 4 , or a salt thereof, or isotopes thereof, wherein the compound comprises a targeting ligand capable of selectively binding to CCK2R and/or CCK2i4svR and a linker that enhances the binding affinity and biodistribution of the compound.
8. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, excipient or diluent.
9. A kit comprising a compound of claim 1 and a pharmaceutically acceptable carrier, excipient or diluent.
10. The kit of claim 9 , wherein the kit is used for imaging of CCK2 receptor expressing cells.
11. The kit of claim 10 , wherein the cells are tumor or cancer cells.
12. The kit of claim 11 , wherein the tumor or cancer is selected from the group consisting of kidney cancers, medullary thyroid cancers, insulinomas, small cell lung cancers, bronchial, and ileal carcinoids, GIST tumors, and colon cancers, hepatocellular carcinomas, and pancreatic cancers.
13. The compound of claim 1 , wherein the salt is a pharmaceutically acceptable salt.
14. The compound of claim 7 , wherein the salt is a pharmaceutically acceptable salt.