PET measurement of D2 and S2 receptor binding of 3-N-[( 2'-18F]fluoroethyl)spiperone in baboon brain

The regional pharmacokinetic behavior in baboon brain of 18F-fluoroethyl- and 18F-fluoropropylspiperone (18FESP, 18FPSP) at specific activities greater than or equal to 1000 Ci/mmol was studied with PET. Four hours after injection of 5-10 mCi 18FESP, uptake in striatum was 0.048% +/- 0.005% of injected dose per cm3, which is almost the same as with 18F- and 11C-methylspiperone. While 18FPSP was taken up in much smaller amounts than 18FESP, striatum to cerebellum activity ratios were quite similar for both ligands (about 9 to 10 at 4 h p.i.). Because of its higher striatal uptake, 18FESP seems to be better suited for PET. Furthermore, relative binding to S2 receptors was much smaller for FESP: competing cold S2 antagonists (ritanserin, ketanserin) did not alter 18FESP binding to striatum, concurrently reducing uptake in frontal cortex by only 15%-20%. With coinjection of increasing amounts of cold FESP, saturation of 18FESP binding to striatum occurred at doses exceeding 10 micrograms per kg. Quantitative analysis of radiolabelled ligand in arterial plasma (decrease to 8% at 4 h p.i.) demonstrated identical metabolic turnover for both ligands. Direct use of binding fractions from the saturation curve resulted in overestimation of the receptor density in striatum. Using the 18FESP plasma concentration time curve and the dynamic uptake data, k3 of a three compartment model could be determined by non linear regression. However, dramatic changes of the dependence of k3 on the specifically bound ligand concentration were observed even at small loading doses of FESP. Estimation of Bmax yielded a D2 receptor density of only 6 pmol per cm3 in baboon striatum.