Synthesis and biological evaluation of I-125/I-123-labelled analogues of citalopram and escitalopram as potential radioligands for imaging of the serotonin transporter

Jacob Madsen, Betina Elfving, Vibe G. Frokjaer, Birgitte R. Kornum, Gerda Thomsen, Lars Martiny, Gitte M. Knudsen

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Two novel radioligands for the serotonin transporter (SERT), [I-125]{3-[5-iodo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]-propyl}-dimethylamine ([I-125]-2) and S-[I-125]{3-[5-iodo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]-propyl}-dimethylamine ([I-125]-(S)-2) were synthesized in a Br/I-125 exchange reaction. Binding experiments in rats yielded K-d values of 0.7 +/- 0.06 and 0.52 +/- 0.02nM for [I-125]-2 and [I-125]-(S)-2, respectively. One hour after intravenous injection of [I-125]-2, 0.34% of the injected dose had accumulated in the brain. The highest hypothalamus-to-cerebellum ratio was reached 2 h after injection of [I-125]-(S)-2 and amounted to 2.4. Pre-treatment experiments with paroxetine resulted in effective reduction of the target-to-cerebellum ratios. The corresponding iodine-123 labelled compound S-[I-123]{3-[5-Iodo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]propyl}- dimethylamine [I-123]-S-2 was investigated in a pig single photon emission computed tomography (SPECT) study. Between 60 and 110 min after IV injection, the midbrain-to-cerebellum ratio was 1.2. However, the uptake did not differ between high-density and medium-density regions questioning the feasibility of the radioligand in imaging cortical SERT distribution in vivo. These data suggest that the iodine-labelled derivatives of citalopram and escitalopram are not superior to another SPECT tracer for the SERT, namely [I-123] ADAM.
    Original languageEnglish
    JournalJournal of Labelled Compounds and Radiopharmaceuticals
    Volume54
    Issue number4
    Pages (from-to)185-190
    ISSN0362-4803
    DOIs
    Publication statusPublished - 2011

    Keywords

    • Hevesy laboratory

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