Preparation and radiosynthesis of [18F]FE@CFN (2-[18F]fluoroethyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate): a potential μ-opioid receptor imaging agent

Abstract

PET imaging of the μ-opioid receptor (OR) is still restricted to [11C]carfentanil ([11C]CFN) but its use is limited due to its short half-life and high agonistic potency. Recently, the radiosynthesis of [18F]fluoroalkyl esters of CFN was proposed, unfortunately yielding products not suitable for human PET due to their low specific activities. Therefore, our rationale was to develop a reliable radiosynthesis of a [18F]fluoroethylated CFN derivative overcoming these drawbacks. The [18F]fluoroethyl ester of carfentanil, [18F]FE@CFN (2-[18F]fluoroethyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate), and its corresponding inactive standard compound were prepared. Purification of [18F]FE@CFN was achieved via a simple solid phase extraction method. [18F]FE@CFN was prepared with excellent purity (> 98%) and sufficient yields. Specific activity surpassed the level required for safe administration. We therefore conclude that our simplified synthesis of [18F]FE@CFN, for the first time, overcomes the shortcomings of [11C]CFN and the previously suggested alternatives, namely, (1) longer half-life; (2) easy production and (3) adequate specific activity, should make a wider application possible. Hence, [18F]FE@CFN may become a valuable PET tracer for the imaging of the μ-OR in human brain and heart.