SYNTHESIS OF A NONPEPTIDE C-11 LABELED SUBSTANCE-P ANTAGONIST FOR PET STUDIES

CP 96,345 is a nonpeptide high affinity antagonist of the substance P (NK1) receptor. The radiosynthesis of [C-11]CP 96,345 suitable for Positron Emission Tomography (PET) applications is described. [C-11]CP 96,345 was prepared by O-methylation of a desmethyl precursor via in situ generation of its phenolate salt. The in vivo tissue distribution of [C-11]CP 96,345 in guinea pigs (n = 2) at 5 and 30 min was determined. Uptake was low in brain (almost-equal-to 0.04% dose/g) and highest ( almost-equal-to 1-2% dose/g) in the spleen and lungs. The present findings indicate that the use of [C-11]CP 96,345 in PET might be more applicable to the study of substance P receptors in peripheral tissues involved with inflammatory disease and arthritis.