19F/18F exchange synthesis for a novel [18F]S1P3‐radiopharmaceutical. (5th June 2013) - Rokka, Johanna
Abstract : 19 F/ 18 F isotope exchange is a useful method to label drug molecules containing 19 F‐fluorine with 18 F without modifying the drug molecule itself. Sphingosine‐1‐phosphate (S1P) is an important cellular mediator that functions by signaling through cell surface receptors. S1P is involved in several cell responses and may be related to many central nervous system disorders, including neural malfunction in Alzheimer's disease. In this study, [ 18 F]1‐benzyl‐ N ‐(3, 4‐difluorobenzyl)‐2‐isopropyl‐6‐(2‐methoxyethoxy)‐1 H ‐indole‐3‐carboxamide, a novel 18 F‐labeled positron emission tomography tracer for the S1P3 receptor, was successfully synthesized using the 19 F/ 18 F isotope exchange reaction. Parameters of the reaction kinetics were studied, and correlations between the initial 18 F‐activity, the amount of precursor, radiochemical yield and specific activity (SA) were determined. Contrary to expectations, high initial 18 F‐activity decreased the radiochemical yield, and only a minor increase of SA occurred. This is most probably due to the complexity of the molecule and the subsequent susceptibility to radiolytic bond disruption. On the basis of the present results, a convenient condition for the 19 F/ 18 F exchange reaction is the use of 2 µmol precursor with 20 GBq of 18 F‐activity. This afforded a radiochemical yield of ~10% with an SA of 0.3 GBq/µmol. Results from this study are of interest for new tracer development where high initial 18 F‐activity and 19 F/ 18 F isotope exchange is used. Abstract : [ 18 F]1‐Benzyl‐ N ‐(3, 4‐difluorobenzyl)‐2‐isopropyl‐6‐(2‐methoxyethoxy)‐1 H ‐indole‐3‐carboxamide ([ 18 F]1 ), a novel 18 F‐labeled positron emission tomography tracer for the S1P3 receptor, was successfully synthesized using 19 F/ 18 F isotope exchange. Contrary to expectations, high initial 18 F‐activity decreased the radiochemical yield, and only a minor increase of specific activity occurred. Results from this study are of interest for new tracer development where 19 F/ 18 F isotope exchange is used.