Synthesis and evaluation of [11C]FR194921 as a nonxanthine-type PET tracer for adenosine A1 receptors in the brain

• Published in: Nuclear medicine and biology Vol. 32; no. 8; pp. 837 - 844
• Main Authors: Matsuya, Takahiro, Takamatsu, Hiroyuki, Murakami, Yoshihiro, Noda, Akihiro, Ichise, Rikiya, Awaga, Yuji, Nishimura, Shintaro
• Format: Journal Article
• Language: English
• Published: United States 01.11.2005
• Subjects: Adenosine A1 Receptor Antagonists; Animals; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes - chemistry; Carbon Radioisotopes - pharmacokinetics; Male; Metabolic Clearance Rate; Organ Specificity; Piperidines - chemistry; Piperidines - pharmacokinetics; Positron-Emission Tomography - methods; Pyridazines - chemistry; Pyridazines - pharmacokinetics; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A1 - metabolism; Staining and Labeling - methods; Tissue Distribution; Whole Body Imaging - methods; Xanthine - pharmacokinetics
• ISSN: 0969-8051
• DOI: 10.1016/j.nucmedbio.2005.06.008

This report describes the synthesis of [11C]2-(1-methyl-4-piperidinyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone ([11C]FR194921), a highly selective, nonxanthine-type adenosine A(1) receptor antagonist, used in brain imaging in rats and conscious monkeys as a potential novel PET tracer. [11C]FR194921 was successfully synthesized in 19 min after [11C]CH3I formation. The radiochemical yield was 38+/-3%; and radioactivity was 4.1+/-0.4 GBq, calculated from end of synthesis; radiochemical purity was higher than 99%; and the specific radioactivity was 25.0+/-8.1 GBq micromol(-1) (n=5). In a rat experiment, the distribution of [11C]FR194921 was higher in the hippocampus, striatum and cerebellum regions. This accumulation was significantly decreased by approximately 50% by pretreatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 receptor antagonist, which indicated specific binding of the radioligand to adenosine A1 receptors. In conscious monkey PET experiments, [11C]FR194921 accumulated in several regions of the brain, especially in the occipital cortex, thalamus and striatum. These results suggest that [11C]FR194921 can be used as an agent for imaging adenosine A1 receptors in vivo by positron emission tomography (PET).