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

6-O-(2-[F-18]fluoroethyl)-6-O-desmethyldiprenorphine ([F-18]DPN) was developed and biologically evaluated. Results of animal experiments, binding studies 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 radiochemical 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, 90 min) after intravenous application of 63 MBq [F-18]DPN (36 GBq/mu mol) and correction for metabolites. Results: [F-18]DPN shows high affinity to opioid receptors. Parametric images (impulse response function at 60 min) of this human study showed a binding pattern of [F-18]DPN equal to that of a control group (n = 9 healthy volunteers) after administration of [C-11]DPN. Conclusion: The advantage of the longer half-life of F-18 Will allow extended scanning periods, more flexible interventions (e.g., displacement studies), and DPN to be available to PET centers without an on-site cyclotron.