title: 19F/18F exchange synthesis for a novel [18F]S1P3-radiopharmaceutical.
abstract: (19)F/(18)F isotope exchange is a useful method to label drug molecules containing (19)F-fluorine with (18)F without modifying the drug molecule itself. Sphingosine-1-phosphate (S1P) is an important cellular mediator that functions by signaling through cell surface receptors. S1P is involved in several cell responses and may be related to many central nervous system disorders, including neural malfunction in Alzheimer's disease. In this study, [(18)F]1-benzyl-N-(3,4-difluorobenzyl)-2-isopropyl-6-(2-methoxyethoxy)-1H-indole-3-carboxamide, a novel (18)F-labeled positron emission tomography tracer for the S1P3 receptor, was successfully synthesized using the (19)F/(18)F isotope exchange reaction. Parameters of the reaction kinetics were studied, and correlations between the initial (18)F-activity, the amount of precursor, radiochemical yield and specific activity (SA) were determined. Contrary to expectations, high initial (18)F-activity decreased the radiochemical yield, and only a minor increase of SA occurred. This is most probably due to the complexity of the molecule and the subsequent susceptibility to radiolytic bond disruption. On the basis of the present results, a convenient condition for the (19)F/(18)F exchange reaction is the use of 2 µmol precursor with 20 GBq of (18)F-activity. This afforded a radiochemical yield of ~10% with an SA of 0.3 GBq/µmol. Results from this study are of interest for new tracer development where high initial (18)F-activity and (19)F/(18)F isotope exchange is used.
authors.affiliation: Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Porthaninkatu 3, FI-20500, Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Rokka
authors.forename: Cesare
authors.initials: C
authors.lastname: Federico
authors.forename: Jori
authors.initials: J
authors.lastname: Jurttila
authors.forename: Anniina
authors.initials: A
authors.lastname: Snellman
authors.forename: Merja
authors.initials: M
authors.lastname: Haaparanta
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
mesh_terms: D005462:Fluorine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling; D008246:Lysophospholipids / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D005462:Fluorine Radioisotopes; D008246:Lysophospholipids; D019275:Radiopharmaceuticals; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: PET chemistry; S1P3 receptor; nucleophilic 18F-fluorination; radiolabelling; sphingosine-1-phosphate