Quantitation of dexfenfluramine/d-norfenfluramine concentration in primate brain using 19F NMR spectroscopy

Fluorine (F-19) magnetic resonance spectroscopy (MRS) was used to quantify the combined concentration of the anorectic drug dexfenfluramine (DF) and its active metabolite d-norfenfluramine (dNF) in rhesus monkey brain. The accuracy of the MRS technique was assessed by comparison with gas chromatography. Brain F-19 MRS signals were converted to brain DF + dNF concentrations after correction for signal relaxation losses and drug distribution in nonbrain tissue, Gas chromatography (GC) was used to assay brain DF and dNF concentrations following MRS evaluation, DF + dNF concentrations measured by F-19 MRS averaged 104 +/- 36 mu M (mean +/- SD) and GC measurements averaged 71 +/- 12 mu M. Correction for the distribution of DF and its metabolites in nonbrain tissue yielded a DF + metabolite brain concentration that was within one standard deviation of the GC-derived value. The concentration of DF plus dNF measured by F-19 MRS was similar to or greater than the value obtained by GC, which indicates that DF and its active metabolite dNF are fully detected by F-19 MRS in primate brain in vivo. The application of these techniques to human subjects should enable the measurement of low micromolar-range brain concentrations of DF and other fluorinated drugs.