An improved one-pot procedure for the preparation of [11C-carbonyl]-WAY100635.

A simple one-pot procedure for the preparation of [11C-carbonyl]-WAY100635, a potent 5HT1A receptor antagonist, was developed. The procedure involves the trapping of 11CO2 in a tetrahydrofuran (THF) solution of cyclohexylmagnesium chloride, elimination of excess Grignard reagents with anhydrous HCl, reaction with SOCl2, and the reaction of the resulting acid chloride with WAY100634 (2 mg) and triethylamine (20 microL) in THF. The total synthesis time is 45 min. Starting from 1326 +/- 173 mCi of 11CO2, the average amount of [11C-carbonyl]-WAY100635 (n = 40) at end-of-synthesis (EOS) was 30 +/- 13 mCi (2.3% radiochemical yield), or 148 +/- 61 mCi (11%) at end-of-bombardment (EOB). The radiochemical purity was >99%, and the specific activity was 3.6 +/- 1.9 Ci/micromol (EOS, n = 40), or 21.3 +/- 9.8 Ci/micromol at EOB. This method is reliable and flexible for routine clinical studies.

[11C]WAY 100635: a radioligand for imaging 5-HT1A receptors with positron emission tomography.

The potent and selective 5-HT1A antagonist WAY 100635 (N-[2-]4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2- pyridinyl)cyclohexanecarboxamide) was radiolabeled with 11C in high specific activity, and the in vivo properties of this radioligand were assessed in the brains of rats and monkeys. Following i.v. tail vein injection in rats, [11C]WAY 100635 rapidly penetrated into brain tissue and was retained over a 30-90 min time period in a manner consistent with the known distribution of 5-HT1A receptors. Pretreatment of rats with the selective 5-HT1A agonist (+/-)-8-OH-DPAT effectively blocked the retention of radioactivity in brain regions known to contain high densities of 5-HT1A receptors. The hippocampus-to-cerebellum radioactivity concentration ratio reached a maximum of 16:1 at 60 min post injection. Following i.v. injection of [11C]WAY 100635 in rhesus monkeys, the concentrations of radioactivity in brain regions were consistent with the reported distribution of 5-HT1A receptors in primates, and the frontal cortex-to-cerebellum ratio reached 5.5:1 at 80 min post injection. Pretreatment of the monkeys with (+/-)-8-OH-DPAT reduced this ratio to 1.4:1, and injection of (+/-)-8-OH-DPAT 20 min after the injection of [11C]WAY 100635 significantly displaced frontal cortex binding. The in vivo properties of [11C]WAY 100635 in rats and monkeys strongly support the future utility of this radioligand for imaging 5-HT1A receptors using positron emission tomography (PET).

Synthesis of a fluorinated fatty acid, dl-erythro-9,10-[18F]difluoropalmitic acid, and biodistribution studies in rats.

9,10-Difluoropalmitic acid (DFPA) labeled with the cyclotron produced, positron emitting radionuclide 18F has been synthesized as a potential analogue of 9,10-[3H]palmitic acid, a fatty acid which has been used to study lipid metabolism in rat brain and pituitary. [18F]DFPA was prepared by the direct and stereoselective addition of [18F]F2 to the double bond of cis-9,10-palmitoleic acid. The fluorination was carried out in FCCl3 at -70 degrees C using a low concentration of F2 (0.5%) in neon. [18F]DFPA has been obtained in radiochemical yields of 12-16% from end-of-bombardment (EOB) in approx. 2.5 h. Chemical and radiochemical purity exceeded 95%, and specific activities calculated to EOB ranged from 500 to 1000 mCi/mmol. [18F]DFPA crosses the blood-brain barrier and is incorporated into rat brain at about twice the level of that of 9,10-[3H]palmitic acid. The synthesis of [18F]DFPA permits us to study the biological disposition and metabolism of a vicinal-difluoro fatty acid.

A controlled comparison of tiaprofenic acid and ibuprofen in osteoarthritis.

A multicentre double-blind crossover study of tiaprofenic acid (600 mg daily) against ibuprofen (1.2 g daily) was undertaken in 77 patients with osteoarthritis to compare their efficacy and tolerance. No difference was found between the two agents, both giving pain relief and being safe and acceptable to the majority of patients. It is concluded that in this short-term study, both agents offer effective and safe treatment for osteoarthritis.