Positron emission tomographic imaging of the cannabinoid type 1 receptor system with [¹¹C]OMAR ([¹¹C]JHU75528): improvements in image quantification using wild-type and knockout mice.
In this study, we assessed the feasibility of using positron emission tomography (PET) and the tracer [¹¹C]OMAR ([¹¹C]JHU75528), an analogue of rimonabant, to study the brain cannabinoid type 1 (CB1) receptor system. Wild-type (WT) and CB1 knockout (KO) animals were imaged at baseline and after pretreatment with blocking doses of rimonabant. Brain uptake in WT animals was higher (50%) than in KO animals in baseline conditions. After pretreatment with rimonabant, WT uptake lowered to the level of KO animals. The results of this study support the feasibility of using PET with the radiotracer [¹¹C]JHU75528 to image the brain CB1 receptor system in mice. In addition, this methodology can be used to assess the effect of new drugs in preclinical studies using genetically manipulated animals.
Institut d’Alta Tecnologia, Parc de Recerca Biomèdica de Barcelona, CRC Corporació Sanitària, Barcelona, Spain.
Raúl
R
Herance
Santiago
S
Rojas
Sergio
S
Abad
Xavier
X
Jiménez
Juan Domingo
JD
Gispert
Olga
O
Millán
Elena
E
Martín-García
Aurelijus
A
Burokas
Miquel Àngel
MÀ
Serra
Rafael
R
Maldonado
Deborah
D
Pareto
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001923:Brain Chemistry; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles / Q000737:chemistry / Q000493:pharmacokinetics; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant
C515663:4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide; D002250:Carbon Radioisotopes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant