title: The possibility of a fully automated procedure for radiosynthesis of fluorine-18-labeled fluoromisonidazole using a simplified single, neutral alumina column purification procedure.
abstract: A novel fully automated radiosynthesis procedure for [(18)F]Fluoromisonidazole using a simple alumina cartridge-column for purification instead of conventionally used semi-preparative HPLC was developed. [(18)F]FMISO was prepared via a one-pot, two-step synthesis procedure using a modified nuclear interface synthesis module. Nucleophilic fluorination of the precursor molecule 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulphonylpropanediol (NITTP) with no-carrier added [(18)F]fluoride followed by hydrolysis of the protecting group with 1M HCl. Purification was carried out using a single neutral alumina cartridge-column instead of semi-preparative HPLC. The maximum overall radiochemical yield obtained was 37.49+/-1.68% with 10mg NITTP (n=3, without any decay correction) and the total synthesis time was 40+/-1 min. The radiochemical purity was greater than 95% and the product was devoid of other chemical impurities including residual aluminum and acetonitrile. The biodistribution study in fibrosarcoma tumor model showed maximum uptake in tumor, 2h post injection. Finally, PET/CT imaging studies in normal healthy rabbit, showed clear uptake in the organs involved in the metabolic process of MISO. No bone uptake was observed excluding the presence of free [(18)F]fluoride. The reported method can be easily adapted in any commercial FDG synthesis module.
authors.affiliation: Radiation Medicine Centre, Bio-Medical Group, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, Mumbai-400 012, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Nandy
authors.forename: M G R
authors.initials: MG
authors.lastname: Rajan
authors.forename: A
authors.initials: A
authors.lastname: Korde
authors.forename: N V
authors.initials: NV
authors.lastname: Krishnamurthy
mesh_terms: D000537:Aluminum Oxide; D000818:Animals; D001331:Automation; D002845:Chromatography; D005354:Fibrosarcoma / Q000175:diagnosis; D005462:Fluorine Radioisotopes; D006801:Humans; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000302:isolation & purification / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole; D000537:Aluminum Oxide