BiOL i~YCHIATRY 1990;29:71 !-714
711
Detection of Psychoactive Drugs In Vivo in Humans Using 19F NMR Spectroscopy Richard A. Komoroski, Joseph E.O. Newton, Craig Karson, David Cardwell, and Jay Sprigg
Introduction
was determined on a I-L round bottom flask containing 1 L of 0.055 mM TFP and 0.075 M A high incidence of extrapyramidal side effects NaCI in 2% agarose an appropriate distance from and frequent treatment failures (Davis and Garver the coil. This phantom is similar in size and 1978) with neuroleptic treatment suggest the need shape to human brain, and electrically loaded for a relevant tissue assay. It has proved surthe coil like a human head. prisingly difficult to correlate serum concentraA vial of 12 mM 2,2,2-(trifluoroethyl)-ptions of neuroleptics with clinical response (Baltoluene sulfonate (TFEPTS) in CDC13 was dessarini et al 1988), possibly due to individual mounted in the coil for peak area normalizavariations in pharmacokinetics or in the retion among spectra and chemical shift refersponse at the active sites in the brain. One soencing. The in vivo specmun was taken from lution is measurement of neuroleptics directly the front or rear of the head with the distance in brain tissue. We report the first observation comparable to that of the phantom. When of trifluoperazine (TFP) in vivo in human head placed about l0 cm above nasion, the active and muscle, and of ~ e antidepressant fluoxetine area of the surface coil cove~ed primarily the in head using ~gF nuclear magnetic resonance cerebral cortex. Apparer, t concentrations were (NMR) spectroscopy. estimated as previously for 7Li (Komorcski et al 1990). Under a constant set of conditions, the spectrum of the phantom and in-plane Methods standard was taken and their area ratio ~as Huorine-19 in vivo NMR spectra were acquired obtained. The ratio of the in vivo peak to the at 60.1 MHz on a GE Signa magnetic resoa~n_ce. in-plane standard was then compared to that imaging system at 1.5 T using a home-built, for the brain phantom. This method minisingle-loop, 16-cm surface coil. Nominal pi/2 mizes some problems inherent in using a surrectangular pulses of 400 ttsec duration and 0.5 face coil (Toffs and Wray 1988). A uniform sec separation were used. The pi/2 pulse power distribution of TFP in tissue is assumed. Magnetic field shimming was performed on ~H in advance by computer for a 20-cm cylindrical From the Departments of Radiology and Pathology (RAK, DC, JS) volume to a resolution of 15-25 Hz. Further, and Psychiatry(JEON, CK), Universityof Arkansas for Medical Sciences,and McClellan Veterans Administration Medical Center in most cases the ins~ument was shimmed on (JEON, CK), Little Rock, AR 72205. the phantom and/or m vivo H20 signal using Address reprint requests to Richard A. Komoroski, Ph.D., NMR Laboratmy, Slot 582, University of Arkansas for Medical Scithe ~9F coil immediately before the run. The ences, 4301 W. Mad~ham Street, Little Rock, AR 72205. typical in vivo ~9F line width of 1.5-2.5 ppm Received May 14, 1990; revised August 26, 1990. © 1991 Society of Biological Psychiatry
0006-3223/91/$03.50
712
Brief Reports
BIOL PSYCHIATRY 1991;29:711-714
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Figure 1. (A) Structure and in vivo 19F NMR spectrum of trifluoperazine in human head with a frontal placement. Number of transients, 1600; line broadening, 30 Hz; spectral width, 6000 Hz in 1024 complex points. The chemical shift scale is referenced to TFEPTS at -74.2 ppm from CCI3F. (B) Structure and V~F spectrum of fluoxetine HCI in vivo in human head. Number of transients, 2400. Remain_ingconditions are as m (A).
was not improved by minor field homogeneity adjustmeats. The ~"F spin-lattice relaxation time (T~) of the phan'om was estimated by standard inversion-recovery to be about 900 msec (3-parameter fit). A homospoil pulse was not necessary because T2*
711
Detection of Psychoactive Drugs In Vivo in Humans Using 19F NMR Spectroscopy Richard A. Komoroski, Joseph E.O. Newton, Craig Karson, David Cardwell, and Jay Sprigg
Introduction
was determined on a I-L round bottom flask containing 1 L of 0.055 mM TFP and 0.075 M A high incidence of extrapyramidal side effects NaCI in 2% agarose an appropriate distance from and frequent treatment failures (Davis and Garver the coil. This phantom is similar in size and 1978) with neuroleptic treatment suggest the need shape to human brain, and electrically loaded for a relevant tissue assay. It has proved surthe coil like a human head. prisingly difficult to correlate serum concentraA vial of 12 mM 2,2,2-(trifluoroethyl)-ptions of neuroleptics with clinical response (Baltoluene sulfonate (TFEPTS) in CDC13 was dessarini et al 1988), possibly due to individual mounted in the coil for peak area normalizavariations in pharmacokinetics or in the retion among spectra and chemical shift refersponse at the active sites in the brain. One soencing. The in vivo specmun was taken from lution is measurement of neuroleptics directly the front or rear of the head with the distance in brain tissue. We report the first observation comparable to that of the phantom. When of trifluoperazine (TFP) in vivo in human head placed about l0 cm above nasion, the active and muscle, and of ~ e antidepressant fluoxetine area of the surface coil cove~ed primarily the in head using ~gF nuclear magnetic resonance cerebral cortex. Apparer, t concentrations were (NMR) spectroscopy. estimated as previously for 7Li (Komorcski et al 1990). Under a constant set of conditions, the spectrum of the phantom and in-plane Methods standard was taken and their area ratio ~as Huorine-19 in vivo NMR spectra were acquired obtained. The ratio of the in vivo peak to the at 60.1 MHz on a GE Signa magnetic resoa~n_ce. in-plane standard was then compared to that imaging system at 1.5 T using a home-built, for the brain phantom. This method minisingle-loop, 16-cm surface coil. Nominal pi/2 mizes some problems inherent in using a surrectangular pulses of 400 ttsec duration and 0.5 face coil (Toffs and Wray 1988). A uniform sec separation were used. The pi/2 pulse power distribution of TFP in tissue is assumed. Magnetic field shimming was performed on ~H in advance by computer for a 20-cm cylindrical From the Departments of Radiology and Pathology (RAK, DC, JS) volume to a resolution of 15-25 Hz. Further, and Psychiatry(JEON, CK), Universityof Arkansas for Medical Sciences,and McClellan Veterans Administration Medical Center in most cases the ins~ument was shimmed on (JEON, CK), Little Rock, AR 72205. the phantom and/or m vivo H20 signal using Address reprint requests to Richard A. Komoroski, Ph.D., NMR Laboratmy, Slot 582, University of Arkansas for Medical Scithe ~9F coil immediately before the run. The ences, 4301 W. Mad~ham Street, Little Rock, AR 72205. typical in vivo ~9F line width of 1.5-2.5 ppm Received May 14, 1990; revised August 26, 1990. © 1991 Society of Biological Psychiatry
0006-3223/91/$03.50
712
Brief Reports
BIOL PSYCHIATRY 1991;29:711-714
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Figure 1. (A) Structure and in vivo 19F NMR spectrum of trifluoperazine in human head with a frontal placement. Number of transients, 1600; line broadening, 30 Hz; spectral width, 6000 Hz in 1024 complex points. The chemical shift scale is referenced to TFEPTS at -74.2 ppm from CCI3F. (B) Structure and V~F spectrum of fluoxetine HCI in vivo in human head. Number of transients, 2400. Remain_ingconditions are as m (A).
was not improved by minor field homogeneity adjustmeats. The ~"F spin-lattice relaxation time (T~) of the phan'om was estimated by standard inversion-recovery to be about 900 msec (3-parameter fit). A homospoil pulse was not necessary because T2*
