Carbon-11-labeled 4-isopropylantipyrine: preparation and biological evaluation as a blood flow tracer in positron emission tomography (PET)

Abstract

Radiolabeled 4-isopropylantipyrine (1) was synthesized and evaluated as a tracer for the measurement of cerebral blood flow (CBF). Methylation of 4-isopropyl-3-methyl-1-phenylpyrazol-5-one (2) with [14C]methyl iodide in acetonitrile gave [14C]-1 in radiochemical yields of 10-20%. Its blood-brain partition coefficient in rats was determined to be 0.62 .+-. 0.03 (mean .+-. SE). Autoradiographic determination of regional cerebral blood flow under normal flow conditions indicated that [14C]-1 gives results essentially identical with those obtained with the widely used tracer [14C]-4-iodoantipyrine ([14C]-IAP). Studies performed in high-flow states indicated that [14C]-1 is not more diffusion limited than [14C]-IAP. A rapid synthesis was therefore developed for the preparation of [14C]-1. Radiochemical yields were increased to 40-50% when the alkylation of 2 with [11C]methyl iodide was performed in dimethyl sulfoxide using solid KOH as a base. Since the 11C-labeled compound can easily be produced in large quantities and since the tracer is not diffusion limited at flow rates commonly observed in normal and most pathological states in man, [11C]-4-isopropylantipyrine will be used for in vivo studies of CBF using positron emission tomography.