Synthesis and preliminary evaluation of [11C]KF15372, a selective adenosine A1 antagonist

Appl Radiat Isot. 1995 Oct;46(10):1009-13. doi: 10.1016/0969-8043(95)00197-l.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Carbon Radioisotopes
  • Isotope Labeling / methods
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred Strains
  • Purinergic P1 Receptor Antagonists*
  • Radioisotope Dilution Technique
  • Radioligand Assay / methods
  • Receptors, Purinergic P1 / metabolism*
  • Time Factors
  • Tissue Distribution
  • Xanthines / chemical synthesis
  • Xanthines / metabolism*
  • Xanthines / pharmacokinetics

Substances

  • Carbon Radioisotopes
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Xanthines
  • 8-(dicyclopropylmethyl)-1,3-dipropylxanthine