RT Journal Article SR Electronic T1 Synthesis and Evaluation of 18F-FE-PEO in Rodents: An 18F-Labeled Full Agonist for Opioid Receptor Imaging JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 299 OP 305 DO 10.2967/jnumed.112.108688 VO 54 IS 2 A1 Patrick J. Riss A1 Young T. Hong A1 János Marton A1 Daniele Caprioli A1 David J. Williamson A1 Valentina Ferrari A1 Neil Saigal A1 Bryan L. Roth A1 Gjermund Henriksen A1 Tim D. Fryer A1 Jeffrey W. Dalley A1 Franklin I. Aigbirhio YR 2013 UL http://jnm.snmjournals.org/content/54/2/299.abstract AB We have investigated the opioid receptor (OR) agonist (20R)-4,5-α-epoxy-6-(2-18F-fluoroethoxy)-3-hydroxy-α,17-dimethyl-α-(2-phenyleth-1-yl)-6,14-ethenomorphinan-7-methanol (18F-FE-PEO) as a candidate OR PET ligand. This tracer is attractive because it combines 18F labeling, is suited to the slow kinetics of high-affinity ligands, and has agonist binding, which has been shown to be more sensitive to changes in OR occupation than is antagonist binding. Methods: Agonist potency and off-target binding were investigated in vitro, and autoradiographic studies on rat brain sections were used to assess binding patterns. Quantification of the tracer in vivo was investigated using small-animal PET in rats with blood sampling. Results: 18F-FE-PEO was obtained by direct nucleophilic radiofluorination and subsequent deprotection with a yield of 28% ± 15%, a specific activity of 52–224 MBq/nmol, and a radiochemical purity of more than 97% (90 min from end of bombardment). In vitro studies showed it to be a full agonist ligand, which selectively binds to OR with high affinity, although it is not selective to a single OR subtype (inhibition constant, 0.4–1.6 nM across OR subtypes). Autoradiography binding patterns were consistent with the known distribution of OR, although nondisplaceable signal typically constituted one third of the signal in OR-dense regions. Although metabolites were present in blood (∼40% of plasma radioactivity was nonparent 3 h after injection), no significant metabolite fraction was found in brain tissue, aiding PET quantification. A plasma input 2-tissue-compartment model provided good fits to the PET data, and regional distribution volumes from the latter correlated well with those from Logan plot analysis (r2 = 0.98). The cerebellum had the lowest distribution volume, but the time–activity curve data could not be adequately fitted with a 1-tissue-compartment model. Reference tissue models using the cerebellum as the reference region did not provide good fits to the data, so blood-based kinetic analysis is recommended. Conclusion: As the first 18F-labeled OR agonist ligand, 18F-FE-PEO is a useful addition to the existing OR ligand portfolio.