F-18 peptides for pre targeted positron emission tomography imaging

#Various embodiments of the present invention concern methods and compositions for radiolabeling peptides with 18F. In particular embodiments, 18F-labeled peptides are of use for various diagnostic applications, such as positron emission tomography (PET). Even more particular embodiments concern compositions and methods of use of [18F]Fluorobenzaldehyde for 18F labeling of peptides.

#Positron emission tomography (PET) is a high resolution, non-invasive, imaging technique for the visualization of human disease. In PET, 511 keV gamma photons produced during positron annihilation decay are detected. In the clinical setting, fluorine-18 (F-18) is one of the most widely used positron-emitting nuclides. F-18 has a half-life (t1/2) of 110 minutes, and emits β+ particles at an energy of 635 keV. It is 97% abundant.

#The short half-life of F-18 has limited or precluded its use with longer-lived specific targeting vectors such as antibodies, antibody fragments, recombinant antibody constructs and longer-lived receptor-targeted peptides. In addition, complicated chemistry has been required to link the inorganic fluoride species to such organic targeting vectors. In typical synthesis methods, an intermediate is radiofluorinated, and the F-18-labeled intermediate is purified for coupling to protein amino groups. See, e.g., Lang et al., Appl. Radiat. Isol., 45 (12): 1155-63 (1994); Vaidyanathan et al., Bioconj. Chem., 5: 352-56 (1994).

#Scheme 1: Conjugation of 4-[18F]Fluorobenzaldehyde to Peptide Via Oxime Linker

#Scheme 2: Conjugation of 4-[18F]Fluorobenzaldehyde to Peptide Via Thiosemicarbazone Linker

#Scheme 3: Conjugation of 4-[18F]Fluorobenzaldehyde to Peptide Via Hydrazone Linker

#As used herein, “a” or “an” may mean one or more than one of an item.

#As used herein, the terms “and” and “or” may be used to mean either the conjunctive or disjunctive. That is, both terms should be understood as equivalent to “and/or” unless otherwise stated.

#An antibody, as described herein, refers to a full-length (i.e., naturally occurring or formed by normal immunoglobulin gene fragment recombinatorial processes) immunoglobulin molecule (e.g., an IgG antibody) or an immunologically active (i.e., specifically binding) portion or analog of an immunoglobulin molecule, like an antibody fragment.