Action and regulation of Beta-adrenergic receptors play a central role in the control and function of the heart. Pertubations in the receptor system have been associated with cardiac malfunctions including disrythmia and sudden death. The precise role of the Betaadrenergic receptor system in heart disease is not well understood because there is no available method for assessing the system except at autopsy. However, the relationship is strongly implied by the success of Betaadrenergic therapy. The dynamic and quantitative nature of positron emission tomography makes it possible to observe receptorligand interactions in vivo with an appropriate labeled ligand. There is reason to believe that the in vivo behavior of the radioliganc can be described as a three compartment system and can be treated by methods of analysis developed for such systems. Preliminary data suggest that there are known ligands whose kinetic properties are within the constraints imposed by the analytical method. We propose to prepare analogs of these ligands (pindolol and carazalol) labeled with the short lived positron emitting radionuclide fluorine18 (t1/2 = 110 munutes). We further propose to use these ligands to test the underlying assumptions of the analytical method. If the method can be shown to be valid then it will be possible to measure the local Betaadrenergic receptor density in humans.i
| Nguyen, V T; Mossberg, K A; Tewson, T J et al. (1990) Temporal analysis of myocardial glucose metabolism by 2-[18F]fluoro-2-deoxy-D-glucose. Am J Physiol 259:H1022-31 |
