An Improved Synthesis of PET Dopamine D₂ Receptors Radioligand [¹¹C]Raclopride

Abstract

An improved synthesis of [¹¹C]raclopride is reported. The precursor desmethyl‐raclopride was synthesized from 3,5‐dichloro‐2,6‐dimethoxybenzoic acid and (S)‐(−)‐2‐aminoethyl‐1‐ethylpyrrolidine via a straightforward, four‐step synthetic approach with 29% overall chemical yield. [¹¹C]Raclopride was prepared by O‐[¹¹C]methylation of the precursor with [¹¹C]methyl triflate and purification with a semi‐preparative HPLC method in 20–34% radiochemical yield, based on [¹¹C]methyl bromide, decay corrected to end of bombardment (EOB).

Keywords:

• [¹¹C]Raclopride
• Synthesis
• Positron emission tomography
• Dopamine D₂ receptors
• Radioligand

Acknowledgments

This work was partially supported by the Indiana 21st Century Research and Technology Fund, and the Lilly Endowment Inc. to the Indiana Genomics Initiative (INGEN) of Indiana University.