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

PET imaging of the mu-opioid receptor (OR) is still restricted to [C-11]carfentanil ([(11)]CFN) but its use is limited due to its short half-life and high agonistic potency. Recently, the radiosynthesis of [F-18]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 [F-18]fluoroethylated CFN derivative overcoming these drawbacks. The [F-18]fluoroethyl ester of carfentanil, [F-18]FE@CFN (2-[F-18]fluoroethyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl) -4-piperidinecarboxylate), and its corresponding inactive standard compound were prepared. Purification of [F-18]FE@CFN was achieved via a simple solid phase extraction method. [F-18]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 [F-18]FE@CFN, for the first time, overcomes the shortcomings of [C-11]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, [F-18]FE@CFN may become a valuable PET tracer for the imaging of the mu-OR in human brain and heart.