Visualization and Quantification of Neurokinin-1 (NK1) Receptors in the Human Brain View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-07

AUTHORS

Jarmo Hietala, Mikko J. Nyman, Olli Eskola, Aki Laakso, Tove Grönroos, Vesa Oikonen, Jörgen Bergman, Merja Haaparanta, Sarita Forsback, Päivi Marjamäki, Pertti Lehikoinen, Michael Goldberg, Donald Burns, Terence Hamill, Wai-Si Eng, Alexandre Coimbra, Richard Hargreaves, Olof Solin

ABSTRACT

PurposeThis study was conducted to develop a new positron emission tomography (PET) method to visualize neurokinin-1 (NK1) receptor systems in the human brain in vivo in order to examine their neuroanatomical distribution and facilitate investigations of the role of substance P, NK1 receptors, and NK1 receptor antagonists in central nervous system (CNS) function and dysfunction.MethodsPET studies were conducted in 10 healthy male volunteers using a novel selective, high-affinity NK1 receptor antagonist labeled with fluorine-18 to very high specific radioactivity (up to 2000 GBq/μmol) [F-18]SPA-RQ. Data were collected in 3D mode for greatest sensitivity. Different modeling methods were compared and regional receptor distributions determined for comparison with in vitro autoradiographic studies using postmortem human brain slices with [F-18]SPA-RQ.ResultsThe studies showed that the highest uptake of [F-18]SPA-RQ was observed in the caudate and putamen. Lower binding was found in globus pallidus and substantia nigra. [F-18]SPA-RQ uptake was also widespread throughout the neocortex and limbic cortex including amygdala and hippocampus. There was very low specific uptake of the tracer in the cerebellar cortex. The distribution pattern was confirmed using in vitro receptor autoradiography with [F-18]SPA-RQ on postmortem human brain slices. Kinetic modeling of the [F-18]SPA-RQ uptake data indicated a binding potential between 4 and 5 in the basal ganglia and between 1.5 and 2.5 in the cortical regions.Conclusions[F-18]SPA-RQ is a novel tool for exploration of the functions of NK1 receptors in man. [F-18]SPA-RQ can be used to define receptor pharmacodynamics and focus dose selection of novel NK1 receptor antagonists in clinical trials thereby ensuring adequate proof of concept testing particularly in therapeutic applications related to CNS dysfunction. More... »

PAGES

262

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11307-005-7001-6

DOI

http://dx.doi.org/10.1007/s11307-005-7001-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019361064

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16155744


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