title: Radiolabeling with fluorine-18 of a protein, interleukin-1 receptor antagonist.
abstract: IL-1RA is a naturally occurring antagonist of the pro-inflammatory cytokine interleukin-1 (IL-1) with high therapeutic promise, but its pharmacokinetic remains poorly documented. In this report, we describe the radiolabeling of recombinant human interleukin-1 receptor antagonist (rhIL-1RA) with fluorine-18 to allow pharmacokinetic studies by positron emission tomography (PET). rhIL-1RA was labeled randomly by reductive alkylation of free amino groups (the epsilon-amino group of lysine residues or amino-terminal residues) using [(18)F]fluoroacetaldehyde under mild reaction conditions. Radiosyntheses used a remotely controlled experimental rig within 100min and the radiochemical yield was in the range 7.1-24.2% (decay corrected, based on seventeen syntheses). We showed that the produced [(18)F]fluoroethyl-rhIL-1ra retained binding specificity by conducting an assay on rat brain sections, allowing its pharmakokinetic study using PET.
authors.affiliation: Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK. cprenant@cyclopharma.fr
authors.forename: C
authors.initials: C
authors.lastname: Prenant
authors.forename: C
authors.initials: C
authors.lastname: Cawthorne
authors.forename: M
authors.initials: M
authors.lastname: Fairclough
authors.forename: N
authors.initials: N
authors.lastname: Rothwell
authors.forename: H
authors.initials: H
authors.lastname: Boutin
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D017472:Receptors, Interleukin-1