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

: Solin O1, Eskola O, Hamill TG, Bergman J, Lehikoinen P, Grönroos T, Forsback S, Haaparanta M, Viljanen T, Ryan C, Gibson R, Kieczykowski G, Hietala J, Hargreaves R, Burns HD

Publisher: Springer

: 2004

: 6

: 373

: 384

: 12

: 1536-1632

DOI: https://doi.org/10.1016/j.mibio.2004.08.001(external)

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.