Tetrazine-trans-cyclooctene ligation for the rapid construction of radionuclide labeled probes
A Diels-Alder adduct of a trans-cyclooctene with a tetrazine is provided, wherein the adduct bears a substituent labeled with a radionuclide. A method of producing a PET or other image of an organ in an animal or human includes forming the Diels-Alder adduct in the animal or human. Trans-cyclooctenes and tetrazines suitable for preparing the adducts are provided.
1. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct.
2. The Diels-Alder adduct of claim 1 , wherein the tetrazine residue of the Diels-Alder adduct is covalently bound to a biomolecule.
3. The Diels-Alder adduct of claim 2 , wherein the biomolecule is in an animal or human.
4. The Diels-Alder adduct of claim 2 , wherein the tetrazine residue is a residue formed by reaction of the biomolecule with a compound according to structure 13
5. The Diels-Alder adduct of claim 2 , wherein the tetrazine residue is a residue formed by reaction of the biomolecule with a compound according to structure 24
6. The Diels-Alder adduct of claim 2 , wherein the radionuclide is 18 F.
7. The Diels-Alder adduct of claim 6 , wherein the trans-cyclooctene residue is a residue of the compound according to structure 9
8. The Diels-Alder adduct of claim 6 , wherein the trans-cyclooctene residue is a residue of the compound according to structure 17
9. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct, wherein the tetrazine residue is a residue of the compound according to structure 5
10. The compound according to structure 9
11. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct, wherein the trans-cyclooctene residue is a residue of the compound according to structure 17
12. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct, wherein the tetrazine residue is a residue of the compound according to structure 13
13. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct, wherein the tetrazine residue is a residue of the compound according to structure 24
14. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct, wherein the tetrazine residue is a residue of the compound according to structure 14
15. The compound according to structure 15
16. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct, wherein the tetrazine residue is a residue of the compound according to structure 18
17. The compound according to structure 19
18. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct, wherein the adduct is the compound according to structure 20
19. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct, wherein the tetrazine residue is a residue of the compound according to structure 22
20. A Diels-Alder adduct of a trans-cyclooctene with a tetrazine, wherein the adduct bears a substituent labeled with a radionuclide, wherein the substituent is a substituent on the trans-cyclooctene residue of the Diels-Alder adduct, wherein the tetrazine residue is a residue of the compound according to structure 29
21. The compound accordina to structure 31