IN-VIVO F-19 SPIN RELAXATION AND LOCALIZED SPECTROSCOPY OF FLUOXETINE IN HUMAN BRAIN

Fluorine-19 NMR spectroscopy was used to monitor the antidepressant drug fluoxetine (and its metabolite norfluoxetine) in vivo in human brain. A quadrature birdcage head coil, developed for operation at 60.1 MHz, yielded a signal from the head 2 to 4 times stronger than for surface coils. It was used to measure the in vivo F-19 spin-lattice relaxation time (T-1) of fluoxetine for five patients by the inversion-recovery technique. The individual T(1)s varied from 149 to 386 ms, which was attributed in part to interindividual differences based on the reproducibility of a phantom T-1. The individual T-1 correlated weakly with approximate brain concentration. A lower limit of 3 to 4 ms was found for the spin-spin relaxation time from line width measurements. Low resolution 4-dimensional spectroscopic imaging confirmed that the single in vivo F-19 resonance for fluoxetine arose primarily from brain. The spectrum of a cerebral hemisphere (in formalin) obtained at autopsy from a patient on 40 mg/day of fluoxetine for 19 weeks was comparable with that seen for patients in vivo. The in vivo signal arose about equally from fluoxetine and the active metabolite norfluoxetine, as demonstrated by the in vitro F-19 NMR spectrum of the lipophilic extract of a small section of brain. In vitro quantitation of frozen samples from three brain regions yielded combined fluoxetine/norfluoxetine concentrations of 12.3 to 18.6 mu g/ml, which is higher than typically determined in vivo, and suggests that the fluorinated drugs may not be 100% visible in vivo.