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

6-O-(2-¹⁸F]fluoroethyl)-6-O-desmethyldiprenorphine ([¹⁸F]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 [¹¹C]DPN. Methods: [¹⁸F]DPN was obtained by ¹⁸F-fluoroethylation of 3- O-trityl-6-O-desmethyldiprenorphine and subsequent deprotection in good radiochemical yields (23% ± 7%; 100 min; 37 TBq/mmol). Binding of [¹⁸F]DPN to μ, κ, and δ opioid receptors was shown by autoradiography studies on rat brain slices. Quantification of cerebral receptor binding in men was performed by spectral analysis of a dynamic PET scan (25 frames, 90 min) after intravenous application of 63 MBq [¹⁸F]DPN (36 GBq/μmol) and correction for metabolites. Results: [¹⁸F]DPN shows high affinity to opioid receptors. Parametric images (impulse response function at 60 min) of this human study showed a binding pattern of [¹⁸F]DPN equal to that of a control group (n = 9 healthy volunteers) after administration of [¹¹C]DPN. Conclusion: The advantage of the longer half-life of ¹⁸F 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.