IN-VIVO EVALUATION OF [F-18] 3-FLUOROPROPYL)-4-(4-CYANOPHENOXYMETHYL)PIPERIDINE - A SELECTIVE SIGMA-1 RECEPTOR RADIOLIGAND FOR PET

3-Fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine (1) has been synthe sized as a selective high affinity (Ki = 4.3 nM) ligand for sigma-1 re ceptors (Ki sigma-1/sigma 2 = 0.03), The corresponding radioligand, F- 18-1, was synthesized via nucleophilic [F-18]fluoride displacement fro m the appropriate N-alkylmesylate precursor. After HPLC purification, F-18-1 was obtained in 56-70% EOB (n = 5) with a specific activity > 7 4,000 MBq/mu mol. In vivo distribution and pharmacological blocking st udies using F-18-1 were performed in male Australian Albino Wistar rat s. F-18-1 exhibited high brain uptake (2.47 +/- 0.37 %ID at 20 min PI) with no significant loss of radioactivity from the brain over the cou rse of the study (4 h), The uptake of radioactivity in the brain, lung , heart, and kidney was reduced significantly by the pre administratio n sigma receptor-binding ligands, indicating the in vivo specificity o f the ligand, The radiotracer also exhibited high uptake (11.14 +/- 1. 99 %ID/g) in B16 melanoma tumours in nude mice, The mean tumour/ tissu e ratios at 4 h for the blood, muscle, lung and brain were 123.8, 7.2, 2.5 and 2.6, respectively. In view of these results, F-18-1 shows pro mise for the in vivo tomographic evaluation of sigma receptors. (C) 19 97 Elsevier Science Inc.