124I-Epidepride: A PET radiotracer for extended imaging of dopamine D2/D3 receptors

Objectives: A new radiotracer, I-124-epidepride, has been developed for the imaging of dopamine D2/3 receptors (D2/3Rs). I-124-Epidepride (half-life of I-124 = 4.2 days) allows imaging over extended periods compared to (18) F-fallypride (half-life of (18) F = 0.076 days) and may maximize visualization of D2/3Rs in the brain and pancreas (allowing clearance from adjacent organs). D2/3Rs are also present in pancreatic islets where they co-localize with insulin to produce granules and may serve as a surrogate marker for imaging diabetes. Methods: I-124-Epidepride was synthesized using N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-tributyltin-2, 3-dimethoxybenzamide and I-124-iodide under no carrier added condition. Rats were used for in vitro and in vivo imaging. Brain slices were incubated with I-124-epidepride (0.75 mu Ci/cc) and nonspecific binding measured with 10 mu M haloperidol. Autoradiograms were analyzed by OptiQuant. I-124-Epidepride (0.2 to 0.3 mCi, iv) was administered to rats and brain uptake at 3 hours, 24 hours, and 48 hours post injection was evaluated. Results: I-124-Epidepride was obtained with 50% radiochemical yield and high radiochemical purity (>95%). I-124-Epidepride localized in the striatum with a striatum to cerebellum ratio of 10. Binding was displaced by dopamine and haloperidol. Brain slices demonstrated localization of I-124-epidepride up until 48 hours in the striatum. However, the extent of binding was reduced significantly. Conclusions: I-124-Epidepride is a new radiotracer suitable for extended imaging of dopamine D2/3 receptors and may have applications in imaging of receptors in the brain and monitoring pancreatic islet cell grafting. (C) 2014 Elsevier Inc. All rights reserved.