6-O-(2-[F-18]Fluoroethyl)-6-O-desmethyldiprenorphine ([F-18]DPN): Synthesis, biologic evaluation, and comparison with [C-11]DPN in humans

6-O-(2-[F-18]fluoroethyl)-6-O-desmethyldiprenorphine ([F-18]DPN) was develo ped and biologically evaluated. Results of animal experiments, binding stud ies in vivo, and a human PET study are reported and compared with those of [C-11]DPN. Methods: [F-18]DPN was obtained by F-18-fluoroethylation of 3-O- trityl-6-O-desmethyldiprenorphine and subsequent deprotection in good radio chemical yields (23% +/- 7%; 100 min; 37 TBq/mmol). Binding of [F-18]DPN to mu, kappa, and delta opioid receptors was shown by autoradiography studies on rat brain slices. Quantification of cerebral opioid receptor binding in men was performed by spectral analysis of a dynamic PET scan (25 frames, 9 0 min) after intravenous application of 63 MBq [F-18]DPN (36 GBq/mu mol) an d correction for metabolites. Results: [F-18]DPN shows high affinity to opi oid receptors. Parametric images (impulse response function at 60 min) of t his human study showed a binding pattern of [F-18]DPN equal to that of a co ntrol group (n = 9 healthy volunteers) after administration of [C-11]DPN. C onclusion: The advantage of the longer half-life of F-18 Will allow extende d scanning periods, more flexible interventions (e.g., displacement studies ), and DPN to be available to PET centers without an on-site cyclotron.