{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:42:11Z","timestamp":1791250931070,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T00:00:00Z","timestamp":1625270400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T00:00:00Z","timestamp":1625270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009379","name":"Interdisziplin\u00e4res Zentrum f\u00fcr Klinische Forschung, Universit\u00e4tsklinikum W\u00fcrzburg","doi-asserted-by":"publisher","award":["F-365"],"award-info":[{"award-number":["F-365"]}],"id":[{"id":"10.13039\/501100009379","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["AL 203\/1-1"],"award-info":[{"award-number":["AL 203\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC\/Transregio 205\/1"],"award-info":[{"award-number":["CRC\/Transregio 205\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2010_EKES.29"],"award-info":[{"award-number":["2010_EKES.29"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e4tsklinikum W\u00fcrzburg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Adrenal tumors represent a diagnostic and therapeutic challenge. Promising results have been obtained through targeting the cytochrome P450 enzymes CYP11B1 and CYP11B2 for molecular imaging, and [<jats:sup>123\/131<\/jats:sup>I]iodometomidate ([<jats:sup>123\/131<\/jats:sup>I]IMTO) has even been successfully introduced as a theranostic agent. As this radiopharmaceutical shows rapid metabolic inactivation, we aimed at developing new improved tracers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Several IMTO derivatives were newly designed by replacing the unstable methyl ester by different carboxylic esters or amides. The inhibition of aldosterone and cortisol synthesis was tested in different adrenocortical cell lines. The corresponding radiolabeled compounds were assessed regarding their stability, in vitro cell uptake, in vivo biodistribution in mice, and their binding specificity to cryosections of human adrenocortical and non-adrenocortical tissue. Furthermore, a first investigation was performed in patients with known metastatic adrenal cancer using both [<jats:sup>123<\/jats:sup>I]IMTO and the most promising compound (R)-1-[1-(4-[<jats:sup>123<\/jats:sup>I]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinylamide ([<jats:sup>123<\/jats:sup>I]IMAZA) for scintigraphy. Subsequently, a first endoradiotherapy with [<jats:sup>131<\/jats:sup>I]IMAZA in one of these patients was performed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We identified three analogues to IMTO with high-affinity binding to the target enzymes and comparable or higher metabolic stability and very high and specific accumulation in adrenocortical cells in vitro and in vivo. Labeled IMAZA exhibited superior pharmacokinetic and imaging properties compared to IMTO in mice and 3 patients, too. An endoradiotherapy with [<jats:sup>131<\/jats:sup>I]IMAZA induced a 21-month progression-free interval in a patient with rapidly progressing ACC prior this therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>We developed the new radiopharmaceutical [<jats:sup>123\/131<\/jats:sup>I]IMAZA with superior properties compared to the reference compound IMTO and promising first experiences in humans.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00259-021-05477-y","type":"journal-article","created":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T01:05:29Z","timestamp":1625274329000},"page":"301-310","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel CYP11B-ligand [123\/131I]IMAZA as promising theranostic tool for adrenocortical tumors: comprehensive preclinical characterization and first clinical experience"],"prefix":"10.1007","volume":"49","author":[{"given":"Britta","family":"Heinze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schirbel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Nannen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Michelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp E.","family":"Hartrampf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bluemel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heribert","family":"Haenscheid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Fassnacht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas K.","family":"Buck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Hahner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,3]]},"reference":[{"key":"5477_CR1","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1530\/EJE-16-0467","volume":"175","author":"M Fassnacht","year":"2016","unstructured":"Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, et al. 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Animal experiments were approved and performed in compliance with the guidelines of the local animal care authorities (Az. 55.2\u20132531.01\u201393\/10). Human scintigraphic imaging with [<sup>123<\/sup>I]IMTO <b>1<\/b> was routine diagnostics based on our manufacturing license. The newly developed radiopharmaceutical [<sup>123\/131<\/sup>I]IMAZA <b>4<\/b> was used according to \u00a713.2b of the German Pharmaceuticals Act. [<sup>131<\/sup>I]IMAZA <b>4<\/b> was administered in a patient with a life-threatening disease and tumor progress following standard treatment after individual ethical counseling by the ethical board of the University Hospital of Wuerzburg, Germany. Written informed consent was obtained prior to diagnostic evaluation and therapy.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AS and SH filed a patent application WO\/2014\/048568 for IMAZA. All other authors declare no potential conflicts of interest.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}