Synthesis, radiolabeling and in vivo evaluation of [¹¹C]RAL-01, a potential phosphodiesterase 5 radioligand

Abstract 

Very few tracers are available for imaging studies of second messenger systems. We developed a radiosynthesis for the phosphodiesterase (PDE) 5 inhibitor [¹¹C]RAL-01. Whole body distribution studies using positron emission tomography (PET) revealed a time-dependant passage through the liver and accumulation of radioactivity in the bile of the Landrace pig. Displaceable binding was readily discerned in the myocardium, and traces of binding were seen in pulmonary tissue, consistent with the use of this class of drug in the treatment of pulmonary hypertension and heart failure. [¹¹C]RAL-01 readily entered the brain and obtained an equilibrium distribution volume of 4–5 ml g⁻¹. Mean parametric images suggested the presence of a small displaceable binding component, but this binding was not significant in the present group of three pigs. Thus, [¹¹C]RAL-01 shows considerable promise for PET studies of biliary elimination and of PDE5 binding in the cardiovascular system. However, analogues of higher affinity may be required for investigations of central nervous system binding sites.

Keywords: Phosphodiesterase 5, PET, Radiosynthesis, Brain, Myocardium, Bile