Dopamine D3 receptor antagonists: the quest for a potentially selective PET ligand. Part 3: Radiosynthesis and in vivo studies.
Compound 1 is a potent and selective antagonist of the dopamine D(3) receptor. With the aim of developing a carbon-11 labeled ligand for the dopamine D(3) receptor, 1 was selected as a potential PET probe. [(11)C]1 was obtained by palladium catalyzed cross coupling using [(11)C]cyanide and 4 with a specific activity of 55.5+/-25.9GBq/micromol (1.5+/-0.7Ci/micromol). [(11)C]1 was tested in porcine and non-human primate models to assess its potential as a radioligand for PET imaging of the dopamine D(3) receptor. We conclude that in both species and despite appropriate in vitro properties, [(11)C]1 does not show any specific signal for the dopamine D(3) receptor.
Bennacef
Idriss
I
GlaxoSmithKline Clinical Imaging Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK.
Salinas
Cristian A
CA
Bonasera
Thomas A
TA
Gunn
Roger N
RN
Audrain
Hélène
H
Jakobsen
Steen
S
Nabulsi
Nabeel
N
Weinzimmer
David
D
Carson
Richard E
RE
Huang
Yiyun
Y
Holmes
Ian
I
Micheli
Fabrizio
F
Heidbreder
Christian
C
Gentile
Gabriella
G
Rossi
Tino
T
Laruelle
Marc
M
D000818:Animals; D002250:Carbon Radioisotopes / Q000737:chemistry; D000882:Haplorhini; D006801:Humans; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013552:Swine
D002250:Carbon Radioisotopes; D048289:Imidazolidines; D008024:Ligands; D010880:Piperidines; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3