[18F]DPA-C5yne, a novel fluorine-18-labelled analogue of DPA-714: radiosynthesis and preliminary evaluation as a radiotracer for imaging neuroinflammation with PET

DPA-C5yne, the lead compound of a novel series of DPA-714 derivatives in which the fluoroethoxy chain linked to the phenylpyrazolopyrimidine scaffold has been replaced by a fluoroalkyn-1-yl moiety, is a high affinity (K-I: 0.35 nM) and selective ligand targeting the translocator protein 18 kDa. In the present work, DPA-C5yne was labelled with no-carrier-added [F-18] fluoride based on a one-step tosyloxy-for-fluorine nucleophilic substitution reaction, purified by cartridge and HPLC, and formulated as an i.v. injectable solution using a TRACERLab FX N Pro synthesizer. Typically, 4.3-5.2GBq of [18F] DPA-C5yne, ready-to-use, chemically and radiochemically pure (> 95%), was obtained with specific radioactivities ranging from 55 to 110GBq/mu mol within 50-60 min, starting from a 30GBq [F-18] fluoride batch (14-17%). LogP and LogD of [F-18] DPA-C5yne were measured using the shake-flask method and values of 2.39 and 2.51 were found, respectively. Autoradiography studies performed on slices of ((R, S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolopropionique (AMPA)-lesioned rat brains showed a high target-to-background ratio (1.9 +/- 0.3). Selectivity and specificity of the binding for the translocator protein was demonstrated using DPA-C5yne (unlabelled), PK11195 and Flumazenil (central benzodiazepine receptor ligand) as competitors. Furthermore, DPA-C5yne proved to be stable in plasma at 37 C for at least 90min.