The present invention discloses 18 FDG conjugated positron emission tomography (PET) imaging agents. In particular, the present invention discloses a cancer specific 18 FDG multimeric PET imaging agents.
1. A contrast agent having a formula selected from the group consisting of:
wherein
R is a targeting ligand;
L 1 and L 2 are linkers;
A is
2. The contrast agent of claim 1 , wherein said linkers are selected from the group consisting of alkane, amino acid, —NHCO(CH 2 ) 5 —, polyethylene glycol and polypropylene glycol.
3. The contrast agent of claim 1 , wherein said contrast agent is in a form of pharmaceutically acceptable salts, hydrates and solvents.
4. The contrast agent of claim 1 , wherein L 1 and L 2 may be same or different.
5. The contrast agent of claim 1 , wherein said targeting ligand is independently selected from the group consisting of a bisphosphonate, an RGD peptide
wherein L 3 is a linking moiety independently selected from the group consisting of alkane, polyethylene glycol and polypropylene glycol.
6. The contrast agent of claim 5 , wherein said bisphosphonate is independently selected from the group consisting of alendronate, etidronate, ibandronate, incadronate, neridronate, olpadronate, phosphonate, pamidronate, risedronate, tiludronate and zoledronate.
7. The contrast agent of claim 5 , wherein said RGD peptide is independently selected from the group consisting of c(RGDfC), c(RADfC), c(RGDfK), c(RADfK), c(RGDfE), c(RADfE), RGDSK, RADSK, RGDS, c(RGDfV), c(RGDyC), c(RADyC), c(RGDyE), c(RGDyK), c(RADyK) and H-E[c(RGDyK)] 2 .
8. A method of making a contrast agent, said method comprising:
(a) providing a multivalent scaffold, wherein said multivalent scaffold is
wherein
R is Boc, Fmoc, Ac, Cbz, Bz or Bn;
L 1 and L 2 are linkers;
and
R 1 is
(b) conjugating said multivalent scaffold with a targeting ligand to yield one or more targeting ligand conjugated multivalent scaffold;
(c) deprotecting an amino protecting group on said one or more targeting ligand conjugated multivalent scaffold to obtain an amine containing targeting ligand conjugated multivalent scaffold;
(d) reacting said amine containing targeting ligand conjugated multivalent scaffold with a 2-[ 18 F]fluoro-2-deoxy-D-glucose in presence of a reducing agent to yield a multivalent 18 FDG amino conjugated imaging agent.
9. The method of claim 8 , wherein said linkers are selected from the group consisting of alkane, amino acid, —NHCO(CH 2 ) 5 —, polyethylene glycol and polypropylene glycol.
10. The method of claim 8 , wherein said contrast agent is in a form of pharmaceutically acceptable salts, hydrates and solvents.
11. The method of claim 8 , wherein said reducing agent is selected from the group consisting of sodium cyanoborohydride, lithium cyanoborohydride, tetrabutylammonium cyanoborohydride, sodium triacetoxyborohydride, tetramethylammonium triacetoxyborohydride, sodium borohydride, lithium borohydride, potassium borohydride, polymer supported borohydride, 2-picoline-borane and borane-pyridine.
12. The method of claim 8 , wherein said targeting ligand is independently selected from the group consisting of a bisphosphonate, an RGD peptide
wherein L 3 is a linking moiety independently selected from the group consisting of alkane, polyethylene glycol and polypropylene glycol.
13. The method of claim 12 , wherein said bisphosphonate is independently selected from the group consisting of alendronate, etidronate, ibandronate, incadronate, neridronate, olpadronate, phosphonate, pamidronate, risedronate, tiludronate and zoledronate.
14. The method of claim 12 , wherein said RGD peptide is independently selected from the group consisting of c(RGDfC), c(RADfC), c(RGDfK), c(RADyK), c(RGDfE), c(RADfE), RGDSK, RADSK, RGDS, c(RGDfV), c(RGDyC), c(RADyC), c(RGDyE), c(RGDyK), c(RADyK), and H-E[c(RGDyK)] 2 .
15. A method of making a contrast agent, said method comprising:
(a) providing a multivalent scaffold, wherein said multivalent scaffold is
wherein
R is Boc, Fmoc, Ac, Cbz, Bz or Bn;
L 1 and L 2 are linkers;
and
R 1 is
(b) conjugating said multivalent scaffold with a targeting ligand to yield one or more targeting ligand conjugated multivalent scaffold;
(c) deprotecting an amino protecting group on said one or more targeting ligand conjugated multivalent scaffold to obtain an amine containing targeting ligand conjugated multivalent scaffold;
(d) treating a 2-[ 18 F]fluoro-2-deoxy-D-glucose with a bromine water to produce a gluconic acid lactone intermediate;
(e) reacting said gluconic acid lactone intermediate with said amine containing targeting ligand conjugated multivalent scaffold to yield a multivalent 18 FDG amido conjugated imaging agent.
16. The method of claim 15 , wherein said linkers are selected from the group consisting of alkane, amino acid, —NHCO(CH 2 ) 5 —, polyethylene glycol and polypropylene glycol.
17. The method of claim 15 , wherein said contrast agent is in a form of pharmaceutically acceptable salts, hydrates and solvents.
18. The method of claim 15 , wherein said targeting ligand is independently selected from the group consisting of a bisphosphonate, an RGD peptide
wherein L 3 is a linking moiety independently selected from the group consisting of alkane, polyethylene glycol and polypropylene glycol.
19. The method of claim 18 , wherein said bisphosphonate is independently selected from the group consisting of alendronate, etidronate, ibandronate, incadronate, neridronate, olpadronate, phosphonate, pamidronate, risedronate, tiludronate and zoledronate.
20. The method of claim 18 , wherein said RGD peptide is independently selected from the group consisting of c(RGDfC), c(RADfC), c(RGDfK), c(RADfK), c(RGDfE), c(RADfE), RGDSK, RADSK, RGDS, c(RGDfV), c(RGDyC), c(RADyC), c(RGDyE), c(RGDyK), c(RADyK), and H-E[c(RGDyK)] 2 .