caa a22 4500 378907166 CHVBK 20180305123532.0 cr unu---uuuuu 161128e20040401xx s 000 0 eng 10.1524/ract.92.4.297.35598 doi (NATIONALLICENCE)gruyter-10.1524/ract.92.4.297.35598 [123/131I]Iodometomidate as a radioligand for functional diagnosis of adrenal disease: synthesis, structural requirements and biodistribution [Elektronische Daten] [A. Schirbel, I. Zolle, F. Hammerschmidt, M. L. Berger, D. Schiller, H. Kvaternik, Chr. Reiners] Metomidate [(R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid methyl ester] (MTO, 1, Fig.1) is a potent and selective inhibitor of the cytochrome P-450 enzyme system in the adrenal cortex. Labelled in the 4-position with radioiodine, (R)-4-[131I]iodometomidate, 2, [131I]IMTO has been evaluated by in-vitro studies and also ex-vivo in rats. [131I]IMTO was synthesized by oxidative radioiododestannylation using a suitable precursor which was prepared by a new stereoselective synthesis. Optimization of the labelling reaction was performed by systematic variation of the most important reaction parameters. Under optimum reaction conditions, a labelling yield of 95% was obtained. In-vitro-stability of the tracer was studied over 8days, indicating slow deiodination (0.27%/h). Displacement studies using [131I]IMTO and rat adrenal membranes revealed the structural requirements for high affinity binding, namely an intact ester group and (R)-configuration of the radioligand. Pharmacokinetic studies in rats showed fast accumulation of [131I]IMTO in the adrenals (approx. 10% ID/g tissue) with an activity plateau for 2hours. Metabolic degradation was indicated by a steady increase of renal activity up to 4hours post injection. Based on target to non-target ratios the highest contrast for imaging of the adrenals was observed between 30 and 60min post injection of [131I]IMTO. We conclude that SPECT using [123I]IMTO will be a promising method for the characterization of adrenal incidentalomas. © 2004 Oldenbourg Wissenschaftsverlag GmbH Laboratory techniques, experiments nationallicence Analytical chemistry nationallicence Inorganic chemistry nationallicence Schirbel A. aut Zolle I. aut Hammerschmidt F. aut Berger M. L. aut Schiller D. aut Kvaternik H. aut Reiners Chr aut Radiochimica Acta/International journal for chemical aspects of nuclear science and technology Oldenbourg Wissenschaftsverlag GmbH 92/4-6/2004(2004-04-01), 297-303 0033-8230 92:4-6/2004<297 2004 92 ract https://doi.org/10.1524/ract.92.4.297.35598 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1524/ract.92.4.297.35598 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schirbel A. aut NATIONALLICENCE 700 1- Zolle I. aut NATIONALLICENCE 700 1- Hammerschmidt F. aut NATIONALLICENCE 700 1- Berger M. L. aut NATIONALLICENCE 700 1- Schiller D. aut NATIONALLICENCE 700 1- Kvaternik H. aut NATIONALLICENCE 700 1- Reiners Chr aut NATIONALLICENCE 773 0- Radiochimica Acta/International journal for chemical aspects of nuclear science and technology Oldenbourg Wissenschaftsverlag GmbH 92/4-6/2004(2004-04-01), 297-303 0033-8230 92:4-6/2004<297 2004 92 ract CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter