Biodistribution of [ 18f] SR144385 and [ 18f] SR147963: selective radioligands for positron emission tomographic studies of brain cannabinoid receptors

• Published in: Nuclear medicine and biology Vol. 27; no. 8; pp. 757 - 762
• Main Authors: Mathews, William B, Scheffel, Ursula, Finley, Paige, Ravert, Hayden T, Frank, Richard A, Rinaldi-Carmona, Murielle, Barth, Francis, Dannals, Robert F
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.11.2000; Elsevier
• Subjects: Administration, Inhalation; Animals; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Cannabinoid antagonist; Cannabinoids - metabolism; Chromatography, High Pressure Liquid; Contrast media. Radiopharmaceuticals; Fluorine Radioisotopes; Fluorine-18; Investigative techniques, diagnostic techniques (general aspects); Isotope Labeling; Ligands; Male; Medical sciences; Mice; Morpholines - administration & dosage; Morpholines - metabolism; Morpholines - pharmacokinetics; Nervous system; PET; Pharmacology. Drug treatments; Piperidines - administration & dosage; Piperidines - metabolism; Piperidines - pharmacokinetics; Pyrazoles - administration & dosage; Pyrazoles - metabolism; Pyrazoles - pharmacokinetics; Radionuclide investigations; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - metabolism; Radiopharmaceuticals - pharmacokinetics; Receptors, Cannabinoid; Receptors, Drug - metabolism; Tissue Distribution; Tomography, Emission-Computed; Mice; Fluorine-18; Cannabinoid antagonist; PET; Radionuclide study; Animal model; Rodentia; Bioavailability; Cannabinoid; Experimental study; Metabolism; Cerebral disorder; Dose activity relation; Vertebrata; Membrane receptor; Mammalia; Mouse; Animal; Central nervous system disease; Pharmacokinetics; Radiopharmaceuticals; Brain (vertebrata); Positron; Emission tomography
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/S0969-8051(00)00152-9

[ 18F] SR144385 and [ 18F] SR147963 were synthesized in a multistep reaction in which fluorine-18 was introduced by nucleophilic halogen displacement on a bromo precursor. The fluorine-18-labeled intermediate was deprotected and coupled with the appropriate alkyl amine to give the final products. Both radioligands had appropriate regional brain distribution for cannabinoid receptors with a target to nontarget ratio of 1.7 for [ 18F] SR147963 and 2.5 for [ 18F] SR144385 at 60 and 90 min postinjection, respectively. The uptake of both tracers was blocked with a 1 mg/kg dose of SR141716A.