[18F]-Fluorethoxy-Repaglinide: A Possible New Ligand for Non-Invasive Estimation of the Pancreatic Islet Cell Mass In-Vivo
Abstract Number: 16-OR
Authors: STEPHAN SCHNEIDER, RALF SCHIRRMACHER, OLIVER THEWS, ABASS A. ALAVI, MATHIAS SCHWANSTECHER, FRANK ROESCH, BJOERN WAENGLER, ESTHER SCHIRRMACHER, CHRISTINA SCHWANSTECHER, PETER J. FEILEN, MATHIAS M. WEBER
Institutions: Mainz, Germany; Braunschweig, Germany; Philadelphia, PA
Results: Imaging and quantification of the islet mass in-vivo remains a challenge. The reason for this inability is the lack of a specific islet cell tracer. Therefore, we present for the first time data concerning the de novo-synthesis, in-vitro and in-vivo evaluation of the high affinity sulfonylurea receptor 1 ligand [18F]-fluorethoxy-repaglinide. First of all, the insulin stimulating capacity and the affinty to the human SUR1 isoform was assessed, to characterize the properties of the tracer. The fluorinated repaglinide-derivative induced a complete monophasic inhibition curve with a Hill coefficient close to 1(1.03) yielding a dissociation constant (KD) of 134, which was comparable to the original-repaglinide. The insulin secretory capacity of the fluorianted-derivative was also well preserved. These positive in-vitro data raise the anticipation that [18F]-fluorethoxy-repaglinide would bind specific and with high-affinty to SUR1 in-vivo. To test this hypothesis we performed a biodistribution study in the rat model. We detected a significant tracer-activity in the pancreas. The highest activity was observed 5 minutes after i.v. injection. Thereafter, a slight decrease of the tracer-activity in the pancreas was observed with a plateau phase between 10 and 30 minutes, followed by a complete washout. Furthermore, we detected a significant activity in the liver but only a very low activity in the kidney, This may be because repaglinide is mainly metabolized by the liver. Afterwards, we showed in a displacement experiment that the activity in the pancreas was specific, because [18F]-fluorethoxy-repaglinide was displaceable by the original repaglinide by 50% of the baseline uptake. In conclusion, these positive data give hope that with [18F]-repaglinide a quantification of the islet cell mass could be possible. In a planned human PET-study this have to be confirmed.