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

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