Fluorination of proteins and peptides for F-18 positron emission tomography
AssigneeImmunomedics, Inc.
InventorGary L. Griffiths
Life of this patent
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Abstract
Thiol-containing peptides can be radiolabeled with fluorine-18 (F-18) by reacting a peptide comprising a free thiol group with an F-18-bound labelling reagent which also has a group that is reactive with thiols. The resulting F-18-labeled peptides may be targeted to a tissue of interest using bispecific antibodies or bispecific antibody fragments having one arm specific for the F-18-labeled peptide or a low molecular weight hapten conjugated to the F-18-labeled peptide, and another arm specific to the targeted tissue. The targeted tissue is subsequently visualized by clinical positron emission tomography.
Claims20
A method for radiolabeling thiol-containing peptides with fluorine-18 (F-18), comprising reacting a peptide comprising a free thiol group with a labelling reagent having the general formula 18F—(CH2)m—CR1R2—(CH2)n—X, wherein:
- n is 0, 1 or 2;
- m is 0, 1 or 2;
- and n+m is 0, 1, or 2;
- X is selected from the group consisting of iodide, bromide, chloride, azide, tosylate, mesylate, nosylate, triflate, unsubstituted maleimide, maleimide substituted with one or two alkyl groups, and 3-sulfo-maleimide;
- and
- R1 and R2 are the same or different and are selected from the group consisting of iodide, bromide, chloride, azide, tosylate, mesylate, nosylate, triflate, hydrogen, —CONH2, carboxyl, hydroxyl, sulfonic acid, tertiary amine, quaternary ammoniumun, unsubstituted alky, substituted alkyl, —COOR′, —CONR′2, or COR′, wherein the substituents of the substituted alkyl groups are selected from the group consisting of —CONH2, carboxyl, hydroxyl, sulfonic acid, tertiary amine and quaternary ammonium and wherein R′ is a C1-C6 alkyl or phenyl.
A method for radiolabeling thiol-containing peptides with fluorine-18 (F-18), comprising reacting a peptide comprising a free thiol group with a F-18 fluorinated alkene, wherein at least one of the two double-bonded carbon atoms bears at least one leaving group selected from the group consisting of iodide, bromide, chloride, azide, tosylate, mesylate, nosylate and triflate.
A method for detecting a tissue comprising:
- (a) administering to a patient a bispecific antibody or antibody fragment comprising an arm that is specific to a target tissue of the patient and another arm that is specific to an F-18-labeled peptide or a low molecular weight hapten conjugated to the F-18-labeled peptide;
- and allowing the bispecific antibody or antibody fragment to bind to the target tissue, and the non-targeted bispecific antibody or antibody fragment to clear;
- (b) administering the F-18-labeled peptide or the hapten conjugate thereof to the patient, and allowing the F-18-labeled peptide or the hapten conjugate thereof to bind to the bispecific antibody or the antibody fragment, and the unbound F-18-labeled peptide or hapten conjugate thereof to clear;
- and
- (c) detecting the F-18-labeled peptide, thereby detecting the target tissue.
Dependencies are inferred from the claim text.