title: Synthesis and preliminary evaluation of [11C]KF15372, a selective adenosine A1 antagonist.
abstract: As a radioligand for mapping the presynaptic adenosine A1 receptors in the central nervous system by PET, [1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine ([11C]KF15372), a selective adenosine A1 antagonist, was prepared by the reaction of 8-dicyclopropylmethyl-3-propylxanthine and [11C]propyl iodide with decay-corrected radiochemical yield of 5% based on the [11C]propyl iodide, radiochemical purity of > 99%, sp. at. of 10-56 GBq/mumol and preparation time of 45-55 min. Another 11C-labeled A1 antagonist with much lower affinity for the A1 receptors, 7-[11C]methyl-KF15372 ([11C]KF17109), was also prepared using [11C]methyl iodide with a decay-corrected radiochemical yield of > 50%. In mice, the brain uptake of [11C]KF15372 (1.91% ID/g at 5 min) decreased gradually with time. Carrier KF15372 competitively reduced the brain uptake to a level (43% of the control) comparable to the brain uptake of [11C]KF17109. On the other hand, an A2 antagonist 3,7-dimethyl-1-propargylxanthine showed no effect on the brain uptake of [11C]KF15372. The results show that [11C]KF15372 has potential as a PET radioligand for mapping the adenosine A1 receptors and that [11C]KF17109 may be a reference compound reflecting the non-specific uptake of the [11C]KF15372.
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D058915:Purinergic P1 Receptor Antagonists; D011865:Radioisotope Dilution Technique; D011869:Radioligand Assay / Q000379:methods; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014970:Xanthines / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C067197:8-(dicyclopropylmethyl)-1,3-dipropylxanthine