# US 7,744,851 B2 · Methods and agents for preparing 18F-radiolabeled fluorinating agents > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,744,851 B2 - Document ID: US7744851B2 - Status: Granted - Kind: B2 - Application number: 11/778,349 - Filed: 2007-07-16 - Published: 2008-01-24 - Granted: 2010-06-29 - Earliest claimed: 2006-07-18 - Assignees: Board of Regents of the University of Nebraska - Inventors: Stephen Gregory DiMagno; Haoran Sun - Web page: https://patentgrep.com/patent/US7744851B2 ## CPC - A61K 51/04: Organic compounds - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The present invention is directed to a method for preparing an anhydrous 18F-radiolabeled fluorinating agent by a nucleophilic reaction of a hydrated 18F-radiolabeled fluoride ion source with an unsaturated carrier compound; treating the 18F-radiolabeled carrier compound to produce a non-aqueous mixture of the 18F-radiolabeled carrier compound in a solvent; and reacting the 18F-radiolabeled carrier compound with a nucleophilic composition in a nucleophilic reaction to produce an anhydrous 18F-radiolabeled fluorinating agent. The present invention is also directed to an anhydrous 18F-radiolabeled fluorinating agent comprising the formula [QnM]x+(18F−)x. Additionally, the present invention is directed to an 18F-radiolabeled fluorinated radiopharmaceutical or an 18F-radiolabeled fluorinated radiotracer prepared by reacting the anhydrous 18F-radiolabeled fluorinating agent with a drug intermediate. The present invention is further directed to methods for treating a disease or imaging a subject using an 18F-radiolabeled fluorinated radiopharmaceutical or an 18F-radiolabeled fluorinated radiotracer. ## Claims ### Claim 1 A method for preparing an anhydrous 18F-radiolabeled fluorinating agent having the formula [QnM]x+(18F−)x, wherein: Q is an organic moiety selected from the group consisting of alkyls, heteroalkyls, aryls, heteroaryls, alkenyls, alkynyls, and polymers; n is an integer such that [QnM] carries at least one formal positive charge; M is a moiety capable of supporting a positive charge; and x is an integer representing the number of formal positives charge(s), +, carried by the [QnM]; the method comprising: (a) a nucleophilic reaction of a 18F-radiolabeled fluoride salt with an unsaturated carrier compound in an anhydrous polar aprotic solvent, wherein the unsaturated carrier compound is selected from the group consisting of: an aromatic compound, an electron deficient aromatic compound, a heteroaromatic compound, and an electron deficient heteroaromatic compound; to produce a 18F-radiolabeled carrier compound; and (b) reacting the 18F-radiolabeled carrier compound with a nucleophilic composition having the formula [QnM]x+Ax″, wherein A is nucleophile, in a second nucleophilic reaction to yield the anhydrous 18F-radiolabeled fluorinating agent having the formula [QnM]x+(18F−)x. ### Claim 2 (depends on 1) A method as set forth in claim 1 wherein M is nitrogen, phosphorus, cobalt, palladium, iodine, arsenic, antimony, ora transition metal complex. ### Claim 3 (depends on 1) A method as set forth in claim 1 wherein the anhydrous polar aprotic solvent is acetonitrile, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, hexasmethylposphoric triamide, diethyl ether, dioxane, dimethoxyethane, methyl tert-butyl ether, N-methylpyrrolidinone, benzonitrile, nitrobenzene, chlorobenzene, or butyronitrile. ### Claim 4 (depends on 1) A method as set forth in claim 1 wherein the unsaturated carrier compound is an electron deficient aromatic compound or an electron deficient heteroaromatic compound. ### Claim 5 (depends on 1) A method as set forth in claim 1 wherein at least one 18F-radiolabeled fluoride ion of the 18F-radiolabeled fluoride salt replaces at least one leaving group of the unsaturated carrier compound by a nucleophilic aromatic substitution reaction. ### Claim 6 (depends on 5) A method as set forth in claim 5 wherein each of the at least one leaving group of the unsaturated carrier compound is a sulfonate, a sulfate, a halide, a carboxylate, a nitrate, a nitrite, a cyanate, an isocyanate, an azide, a thiocyanate, an ether, an amine, a phosphine, or a nitrogen molecule. ### Claim 7 (depends on 1) A method as set forth in claim 1 wherein A is a cyanide, a thiocyanate, a phenoxide, an arylalkoxide, a thiolates, an enolate, an imide anion, amide anion, an isothiocyanate, a phosphine, or an amine. ### Claim 8 An anhydrous 18F-radiolabeled fluorinating agent having the formula [QnM]x+(18F−)x, wherein: M is a moiety capable of supporting a positive charge; Q is an independently varied organic moiety selected from the group consisting of alkyls, heteroalkyls, aryls, heteroaryls, alkenyls, alkynyls, and polymers; n is an integer such that [QnM] carries at least one formal positive charge; and x is an integer representing the number of formal positive charge(s), +, carried by the [QnM]. ### Claim 9 (depends on 1) A method for preparing an 18F-radiolabeled fluorinated radiopharmaceutical comprising preparing an anhydrous 18F-radiolabeled fluorinating agent having the formula [QnM]x+(18F−)x in accordance with the method of claim 1 and reacting the anhydrous 18F-radiolabeled fluorinating agent with a drug intermediate to produce an 18F-radiolabeled fluorinated radiopharmaceutical. ### Claim 10 (depends on 1) A method for preparing an 18F-radiolabeled fluorinated radiotracer comprising preparing an anhydrous 18F-radiolabeled fluorinating agent having the formula [QnM]x+(18F−)x in accordance with the method of claim 1 and reacting the anhydrous 18F-radiolabeled fluorinating agent with a drug intermediate to produce the 18F-radiolabeled fluorinated radiotracer. ### Claim 11 (depends on 1) An anhydrous 18F-radiolabeled fluorinating agent prepared by the method of claim 1. ### Claim 12 (depends on 9) An 18F-radiolabeled fluorinated radiopharmaceutical prepared by the method of claim 9. ### Claim 13 (depends on 10) An 18F-radiolabeled fluorinated radiotracer prepared by the method of claim 10. ### Claim 14 (depends on 1) A method for imaging a subject by positron electron tomography using an 18F-radiolabeled fluorinated radiotracer comprising preparing an anhydrous 18F-radiolabeled fluorinating agent having the formula [QnM]x+(18F−)x in accordance with the method of claim 1, reacting the anhydrous 18F-radiolabeled fluorinating agent with a drug intermediate to produce the 18F-radiolabeled fluorinated radiotracer, administering to a subject the 18F-radiolabeled fluorinated radiotracer and, imaging the subject by positron electron tomography. ### Claim 15 (depends on 1) A method for treating a disease using an 18F-radiolabeled fluorinated radiopharmaceutical comprising preparing an anhydrous 18F-radiolabeled fluorinating agent having the formula [QnM]x+(18F−)x in accordance with the method of claim 1, reacting the anhydrous 18F-radiolabeled fluorinating agent with a drug intermediate to produce the 18F-radiolabeled fluorinated radiopharmaceutical and administering to a subject the 18F-radiolabeled fluorinated radiopharmaceutical. ### Claim 16 (depends on 14) A method as set forth in claim 14 wherein the subject is a human or an animal. ### Claim 17 (depends on 15) A method as set forth in claim 15 wherein the subject is a human or an animal. ### Claim 18 (depends on 1) A method as set forth in claim 1 wherein the anhydrous polar aprotic solvent is acetonitrile or dimethyl sulfoxide. ### Claim 19 (depends on 8) An anhydrous 18F-radiolabeled fluorinating agent as set forth in claim 8 wherein M is nitrogen, phosphorus, cobalt, palladium, iodine, arsenic, antimony, or a transition metal complex. ### Claim 20 (depends on 8) An anhydrous 18F-radiolabeled fluorinating agent as set forth in claim 8 wherein A is a cyanide, a thiocyanate, a phenoxide, an arylalkoxide, a thiolates, an enolate, an imide anion, amide anion, an isothiocyanate, a phosphine, or an amine.