Syntheses and specific activity determinations of no-carrier-added fluorine-18-labeled neuroleptic drugs

A general method for the syntheses of no-carrier-added (NCA) ¹⁸F-labeled butyrophenone neuroleptics-benperidol, haloperidol, spiroperidol, and pipamperone is described. These ¹⁸F-labeled neuroleptic drugs are synthesized by a multistep synthesis in an overall radiochemical yield of 10-20% at end of bombardment (EOB) in a synthesis time of 90 min from EOB. The sequence involves the synthesis of NCA p-[¹⁸F]fluorobenzonitrile from NCA [¹⁸F]-fluoride and p-nitrobenzonitrile using the nucleophilic aromatic substitution reaction (¹⁸F for NO₂). p-[¹⁸F]Fluorobenzonitrile is rapidly converted to γ-chloro-p-[¹⁸F]fluorobutyrophenone which is alkylated with appropriate amines to give NCA ¹⁸F-labeled benperidol, haloperidol, spiroperidol, and pipamperone. The final product is purified by preparative high performance liquid chromatography (HPLC). The ¹⁸F solution used in the synthesis as determined by ion chromatography contains 15.3 ± 9.0 nmol of stable fluoride. The specific activities of the resulting butyrophenone neuroleptics were determined to be 3 Ci/μmol (at EOB) (range 1-6 Ci/μmol) as determined by radioreceptor assay and HPLC assay.