11C-Radiosynthesis and preliminary human evaluation of the disposition of the ACE inhibitor [11C]zofenoprilat |
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Authors: | Matarrese Mario Salimbeni Aldo Turolla Elia Anna Turozzi Damiano Moresco Rosa Maria Poma Davide Magni Fulvio Todde Sergio Rossetti Claudio Sciarrone Maria Teresa Bianchi Giuseppe Kienle Marzia Galli Fazio Ferruccio |
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Institution: | Institute of Molecular Bioimaging and Physiology-CNR, University of Milano/Bicocca, Institute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. |
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Abstract: | (4S)-1-(S)-3-Mercapto-2-methylpropanoyl]-4-phenylthio-L-proline (Zofenoprilat, 2), the active metabolite of the potent ACE inhibitor Zofenopril Calcium (1), was labelled with carbon-11 (t1/2=20.4 min) to evaluate its pharmacokinetics behaviour in human body using Positron Emission Tomography (PET). 11C]2 labelling procedures were based on the use of immobilized Grignard reagent and the acylation of (S)-4-phenylthio-L-proline methyl ester (5) with 11C-labelled methacryloyl chloride, followed by a Michael addition with thiobenzoic acid. The radiochemical yield was 5-10% (EOB, decay corrected) and specific radioactivity ranged from 0.5 to 1.5 Ci/micromol (18.5-55.5 GBq/micromol). Preliminary in vivo human evaluation of 11C]2 showed that the drug accumulates in organs which express high levels of ACE, like lungs and kidneys, and in organs involved in drug metabolism such as the liver and gall bladder. Results of the distribution of 11C]2 showed a measurable concentration of the drug in the target tissues such as the kidney and to a minor extent, the heart, where it can afford organ protection. |
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