Hydroxamic acid type contrast agent containing radioisotope fluoride, preparation method and application thereof

A method for preparing a hydroxamic acid-based contrast agent containing an isotope of fluorine, comprising:

• Step I:
• preparing a precursor by dissolving 2-methyl-4-nitrophenol, methyl 4-bromobutyrate, and potassium carbonate in dimethyl formamide, wherein the molar ratio of the 2-methyl-4-nitrophenol, the 4-methyl bromobutyrate and the potassium carbonate is 8.2:11:20, and reacting at 60-90° C. for 12-36 hrs, wherein the precursor has a structure of Formula (I):
• wherein R1 is nitro, and R2 is methoxy;
• then adding ethyl acetate, and extracting with a saturated sodium bicarbonate solution, an aqueous hydrochloric acid solution, and a saturated saline;
• and collecting the organic layer, removing water, concentrating under reduced pressure, filtering, and purifying by column chromatography on silica gel, to obtain the precursor as a yellow solid;
• Step II:
• fluorinating the prepared precursor to produce an intermediate product wherein the intermediate product is a compound having a structure of Formula (II):
• wherein R1 is radioactive fluorine-18 (18F) or isotope fluorine-19 (19F), and R2 is methoxy;
• and
• Step III:
• subjecting the intermediate product to a hydroxamic acid forming reaction, to form the final product which has a structure of Formula (III):
• wherein R1 is radioactive fluorine-18 (18F) or isotope fluorine-19 (19F), and R2 is —(NH)OH, and wherein the hydroxamic acid forming reaction comprises reacting the intermediate product, hydroxylamine, and sodium hydroxide for 5-20 min at 30-50° C.