ABP688, a novel selective and high affinity ligand for the labeling of mGlu5 receptors: identification, in vitro pharmacology, pharmacokinetic and biodistribution studies.
[(11)C]ABP688 (2) has recently been demonstrated to be a useful PET tracer for in vivo imaging of the metabotropic glutamate receptors type 5 (mGluR5) in rodents. We describe here the identification and preclinical profiling of ABP688 and its tritiated version [(3)H]ABP688, and show that its high affinity (K(d)=2nM), selectivity, and pharmacokinetic properties fulfill all requirements for development as a PET tracer for clinical imaging of the mGlu5 receptor.
Hintermann
Samuel
S
Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland.
Vranesic
Ivo
I
Allgeier
Hans
H
Brülisauer
Armin
A
Hoyer
Daniel
D
Lemaire
Michel
M
Moenius
Thomas
T
Urwyler
Stephan
S
Whitebread
Steven
S
Gasparini
Fabrizio
F
Auberson
Yves P
YP
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006224:Cricetinae; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008024:Ligands; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010091:Oximes / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011725:Pyridines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000187:drug effects*; D014018:Tissue Distribution
D001798:Blood Proteins; D018690:Excitatory Amino Acid Agonists; D007202:Indicators and Reagents; D008024:Ligands; D010091:Oximes; D010716:Phosphatidylinositols; D011725:Pyridines; D016318:Quisqualic Acid; D019275:Radiopharmaceuticals; D018092:Kainic Acid Receptors; C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; C121465:6-methyl-2-(phenylethynyl)pyridine