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.
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.
Authors: Fumihiko Yasuno; Sandra M Sanabria; Donald Burns; Richard J Hargreaves; Subroto Ghose; Masanori Ichise; Frederick T Chin; Cheryl L Morse; Victor W Pike; Robert B Innis Journal: Synapse Date: 2007-04 Impact factor: 2.562
Authors: David R Sprague; Frederick T Chin; Jeih-San Liow; Masahiro Fujita; H Donald Burns; Richard Hargreaves; James B Stubbs; Victor W Pike; Robert B Innis; P David Mozley Journal: J Nucl Med Date: 2007-01 Impact factor: 10.057
Authors: Sean R Donohue; Joseph H Krushinski; Victor W Pike; Eyassu Chernet; Lee Phebus; Amy K Chesterfield; Christian C Felder; Christer Halldin; John M Schaus Journal: J Med Chem Date: 2008-09-25 Impact factor: 7.446
Authors: Yota Fujimura; Fumihiko Yasuno; Amanda Farris; Jeih-San Liow; Marilla Geraci; Wayne Drevets; Daniel S Pine; Subroto Ghose; Alicja Lerner; Richard Hargreaves; H Donald Burns; Cheryl Morse; Victor W Pike; Robert B Innis Journal: Biol Psychiatry Date: 2009-02-07 Impact factor: 13.382
Authors: Saskia P A Wolfensberger; Bart N M van Berckel; Anu J Airaksinen; Kaoru Maruyama; Mark Lubberink; Ronald Boellaard; William D H Carey; Wieb Reddingius; Dick J Veltman; Albert D Windhorst; Josée E Leysen; Adriaan A Lammertsma Journal: Mol Imaging Biol Date: 2009-03-31 Impact factor: 3.488