Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK1 receptor quantitation: ([18F]SPA-RQ).
OBJECTIVE
To develop and characterize a radiolabelled Substance-P antagonist useful for quantitation of neurokinin-1 receptors in the brain via PET imaging.


METHODS
[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.


CONCLUSIONS
[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.
Solin
Olof
O
Turku PET Centre, Turku, Finland.
Eskola
Olli
O
Hamill
Terence G
TG
Bergman
Jörgen
J
Lehikoinen
Pertti
P
Grönroos
Tove
T
Forsback
Sarita
S
Haaparanta
Merja
M
Viljanen
Tapio
T
Ryan
Christine
C
Gibson
Raymond
R
Kieczykowski
Gerard
G
Hietala
Jarmo
J
Hargreaves
Richard
R
Burns
H Donald
HD
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D006168:Guinea Pigs; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D018040:Receptors, Neurokinin-1 / Q000032:analysis* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013057:Spectrum Analysis; D013373:Substance P / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D006842:Hydrocarbons, Brominated; D006845:Hydrocarbons, Fluorinated; D018040:Receptors, Neurokinin-1; C425968:bromofluoromethane; D013373:Substance P