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Quantitation of dexfenfluramine/d-norfenfluramine concentration in primate brain using 19F NMR spectroscopy.
Magn Reson Med. 1998 Jan; 39(1):149-54.MR

Abstract

Fluorine (19F) 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 19F 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 19F MRS averaged 104 +/- 36 microM (mean +/- SD) and GC measurements averaged 71 +/- 12 microM. 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 19F 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 19F 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.

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Authors+Show Affiliations

Christensen JD
Brain Imaging Center, McLean Hospital, Belmont, Massachusetts, USA.
Babb SM
No affiliation info available
Cohen BM
No affiliation info available
Renshaw PF
No affiliation info available

MeSH

AnimalsAppetite DepressantsBrainBrain ChemistryDisease Models, AnimalFemaleFenfluramineFluorine RadioisotopesMacaca mulattaMagnetic Resonance SpectroscopyMaleNorfenfluramineSensitivity and SpecificitySignal Processing, Computer-Assisted

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9438448

Citation

Christensen, J D., et al. "Quantitation of Dexfenfluramine/d-norfenfluramine Concentration in Primate Brain Using 19F NMR Spectroscopy." Magnetic Resonance in Medicine, vol. 39, no. 1, 1998, pp. 149-54.
Christensen JD, Babb SM, Cohen BM, et al. Quantitation of dexfenfluramine/d-norfenfluramine concentration in primate brain using 19F NMR spectroscopy. Magn Reson Med. 1998;39(1):149-54.
Christensen, J. D., Babb, S. M., Cohen, B. M., & Renshaw, P. F. (1998). Quantitation of dexfenfluramine/d-norfenfluramine concentration in primate brain using 19F NMR spectroscopy. Magnetic Resonance in Medicine, 39(1), 149-54.
Christensen JD, et al. Quantitation of Dexfenfluramine/d-norfenfluramine Concentration in Primate Brain Using 19F NMR Spectroscopy. Magn Reson Med. 1998;39(1):149-54. PubMed PMID: 9438448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantitation of dexfenfluramine/d-norfenfluramine concentration in primate brain using 19F NMR spectroscopy. AU - Christensen,J D, AU - Babb,S M, AU - Cohen,B M, AU - Renshaw,P F, PY - 1998/1/23/pubmed PY - 1998/1/23/medline PY - 1998/1/23/entrez SP - 149 EP - 54 JF - Magnetic resonance in medicine JO - Magn Reson Med VL - 39 IS - 1 N2 - Fluorine (19F) 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 19F 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 19F MRS averaged 104 +/- 36 microM (mean +/- SD) and GC measurements averaged 71 +/- 12 microM. 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 19F 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 19F 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. SN - 0740-3194 UR - https://www.unboundmedicine.com/medline/citation/9438448/Quantitation_of_dexfenfluramine/d_norfenfluramine_concentration_in_primate_brain_using_19F_NMR_spectroscopy_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0740-3194&date=1998&volume=39&issue=1&spage=149 DB - PRIME DP - Unbound Medicine ER -