Results
Title

Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK<sub>1</sub> receptor quantitation: ([<sup>18</sup>F]SPA-RQ)

Authors

Solin, Olof; Eskola, Olli; Hamill, Terence G.; Bergman, Jörgen; Lehikoinen, Pertti; Grönroos, Tove; Forsback, Sarita; Haaparanta, Merja; Viljanen, Tapio; Ryan, Christine; Gibson, Raymond; Kieczykowski, Gerard; Hietala, Jarmo; Hargreaves, Richard; Burns, H. Donald; Bergman, Jörgen; Grönroos, Tove

Abstract

Purpose: To develop and characterize a radiolabelled Substance-P antagonist useful for quantitation of neurokinin-1 receptors in the brain via PET imaging. Procedure: [18F]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 [18F]bromofluoromethane. Removal of the BOC protecting group with trifluoroacetic acid gave [18F]SPA-RQ. Results: SPA-RQ has high affinity for human, rhesus monkey and guinea pig NK1 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 NK1 receptors in the striatum and cortex. Conclusion: [18F]SPA-RQ is a potent, high affinity Substance-P antagonist that can be conveniently labeled with high specific activity using [18F]fluoromethylbromide. This tracer is a useful tool for noninvasive imaging of central NK1 receptors.

Subjects

TACHYKININS; NEUROPEPTIDES; ALKYLATION; ANIONS

Publication

Molecular Imaging & Biology, 2004, Vol 6, Issue 6, p373

ISSN

1536-1632

Publication type

Academic Journal

DOI

10.1016/j.mibio.2004.08.001