Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK1 receptor quantitation:: ([18F]SPA-RQ)

PURPOSE: To develop and characterize a radiolabelled Substance-P antagonist useful for quantitation of neurokinin-1 receptors in the brain via PET imaging. PROCEDURE: [F-18]SPA-RQ (Substance-P antagonist- receptor quantifier) was synthesized in good yield and high specific activity by alkylation of a BOC protected phenolate anion using [F-18]bromofluoromethane. Removal of the BOC protecting group with trifluoroacetic acid gave [F-18]SPA-RQ. RESULTS: SPA-RQ has high affinity for human, rhesus monkey and guinea pig NKI receptors (h-IC50 = 67 pM) and has a log P value of 1.8. Biodistribution studies in guinea pig showed that this tracer penetrates the blood-brain barrier and selectively labels NKI receptors in the striatum and cortex. CONCLUSION: [F-18]SPA-RQ is a potent, high affinity Substance-P antagonist that can be conveniently labeled with high specific activity using [F-18]fluoromethylbromide. This tracer is a useful tool for noninvasive imaging of central NKI receptors. (C) 2004 Elsevier Inc. All rights reserved.