Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules

摘要

The present application discloses compositions and methods of synthesis and use of 18F or 19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the labeled molecule may be used for imaging in a subject without purification after labeling.

主权项

1. A composition comprising an 19F- or 18F-labeled targeting molecule comprising a bifunctional chelating agent of the structure wherein R1 and R2 are independently selected from the group consisting of
—CH2—COOH—CH2—CH2—OH—CH(CH3)—COOH—CH(C6H5)—COOH and R3 is selected from the group consisting of: wherein M selected from the group consisting of aluminum, gallium, indium, lutetium and thallium and X is 19F orl8F, wherein n =1-9 and wherein R═F, CH2F, CHF2, CH3 or OCF3.