| Abstract
| - Identification and pharmacological characterization of two new selective δ-opioid receptor antagonists, derived from the Dmt-Tic pharmacophore, of potential utility in positron emission tomography (PET) imaging are described. On the basis of its high δ selectivity, H-Dmt-Tic-ϵ-Lys(Z)-OH (reference compound 1) is a useful starting point for the synthesis of 18F-labeled compounds prepared by the coupling of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) with Boc-Dmt-Tic-ϵ-Lys(Z)-OH under slightly basic conditions at 37 °C for 15 min, deprotection with TFA, and HPLC purification. The total synthesis time was 120 min, and the decay-corrected radiochemical yield of [18F]-1 was about 25-30% (n = 5) starting from [18F]SFB (n = 5) with an effective specific activity about 46 GBq/µmol. In vitro autoradiography studies showed prominent uptake of [18F]-1 in the striatum and cortex with significant blocking by 1 and UFP-501 (selective δ-opioid receptor antagonist), suggesting high specific binding of [18F]-1 to δ-opioid receptors. Noninvasive microPET imaging studies revealed the absence of [18F]-1 in rat brain, since it fails to cross the blood−brain barrier. This study demonstrates the suitability of [18F]-1 for imaging peripheral δ-opioid receptors.
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