Imaging methods using
The invention relates to water soluble 18 F-prosthetic groups and the synthesis and use of 18 F-labeled biological molecules containing the 18 F-prosthetic groups for imaging various processes within the body, for detecting the location of molecules associated with disease pathology, and for monitoring disease progression are disclosed.
1. A method of visualizing a target molecule in a subject, comprising
a. administering to the subject an imaging agent that binds specifically to the target molecule at a dose of about 3-10 mCi (100-333 MBq); and
b. conducting a PET scan of the subject about 30-120 minutes after step (a), wherein the imaging agent comprises a comprises a fibronectin type III domain linked to a radioactive PET tracer by a bifunctional conjugating moiety (BFC) comprising a reactive group that forms a covalent bond with an amine, carboxyl, carbonyl or thiol functional group on the protein.
2. The method of claim 1 , wherein the subject has at least one tumor.
3. The method of claim 2 , wherein the level of the target molecule the at least one tumor of the subject is visualized.
4. The method of claim 3 , for determining whether a subject is likely to respond to a treatment with an immuno-oncology agent.
5. The method of claim 1 , wherein the radioactive PET tracer is 18 F.
6. The method of claim 1 , wherein the BFC is a cyclooctyne comprising a reactive group that forms a covalent bond with an amine, carboxyl, carbonyl or thiol functional group on the protein.
7. The method of claim 6 , wherein the cyclooctyne is selected from the group consisting of dibenzocyclooctyne (DIBO), biarylazacyclooctynone (BARAC), dimethoxyazacyclooctyne (DIMAC) and dibenzocyclooctyne (DBCO).
8. The method of claim 1 , wherein the BFC further comprises a polyethylene glycol (PEG) y spacer arm, wherein y is an integer from 1 to 8.
9. The method of claim 1 , wherein the BFC is DBCO-PEG4-NHS-Ester, DBCO-Sulfo-NHS-Ester, DBCO-PEG4-Acid, DBCO-PEG4-Amine or DBCO-PEG4-Maleimide.
10. The method of claim 9 , wherein the cystein residue is at the C-terminus of the protein.
11. The method of claim 1 , wherein the BFC is covalently linked to a thiol group on a cysteine residue of the protein.
12. The method of claim 1 , wherein the Fn3 domain is a tenth fibronectin type III domain ( 10 Fn3).
13. The method of 4 , wherein the subject is being treated with a therapeutic agent.
14. The method of claim 13 , wherein the therapeutic agent is an immunotherapy agent.
15. The method of claim 14 , wherein the immunotherapy agent is a PD-1 antagonist.
16. The method of claim 15 , wherein the PD-1 antagonist is an anti-PD-1 antibody.
17. The method of claim 16 , wherein the anti-PD-1 antibody is nivolumab or pembrolizumab or atezolizumab.
18. The method claim 13 , wherein the imaging agent is administered to the subject prior to the first administration of the therapeutic agent.
19. The method of claim 13 , wherein the imaging agent is administered to the subject after administration of the first dose of therapeutic agent.
20. The method of claim 13 , wherein the imaging agent is administered to the subject prior to administration of the first dose of therapeutic agent and 1-7 days after administration of the first dose of therapeutic agent.