{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T02:21:37Z","timestamp":1786760497640,"version":"build-2736575974"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T00:00:00Z","timestamp":1712361600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T00:00:00Z","timestamp":1712361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100013362","name":"Swiss Cancer Research Foundation","doi-asserted-by":"publisher","award":["KFS-3170-02-2013"],"award-info":[{"award-number":["KFS-3170-02-2013"]}],"id":[{"id":"10.13039\/501100013362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023862","name":"Nora van Meeuwen H\u00e4fliger Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023862","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008375","name":"University of Basel","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008375","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EJNMMI Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation. Nevertheless, relatively low tumor radiation doses in patients indicate limited stability in humans. We aimed at evaluating the effect of sacubitril, an inhibitor of the neutral endopeptidase 1, on the stability and absorbed doses to tumors and organs by the cholecystokinin-2 receptor agonist [<jats:sup>177<\/jats:sup>Lu]Lu-PP-F11N in patients. In this prospective phase 0 study eight consecutive patients with advanced medullary thyroid carcinoma and a current somatostatin receptor subtype 2 PET\/CT scan were included. Patients received two short infusions of\u2009~\u20091\u00a0GBq [<jats:sup>177<\/jats:sup>Lu]Lu-PP-F11N in an interval of\u2009~\u20094\u00a0weeks with and without Entresto<jats:sup>\u00ae<\/jats:sup> pretreatment in an open-label, randomized cross-over order. Entresto<jats:sup>\u00ae<\/jats:sup> was given at a single oral dose, containing 48.6\u00a0mg sacubitril. Adverse events were graded and quantitative SPECT\/CT and blood sampling were performed. Absorbed doses to tumors and relevant organs were calculated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Pretreatment with Entresto<jats:sup>\u00ae<\/jats:sup> showed no additional toxicity and increased the stability of [<jats:sup>177<\/jats:sup>Lu]Lu-PP-FF11N in blood significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Median tumor-absorbed doses were 2.6-fold higher after Entresto<jats:sup>\u00ae<\/jats:sup> pretreatment (0.74 vs. 0.28\u00a0Gy\/GBq, <jats:italic>P<\/jats:italic>\u2009=\u20090.03). At the same time, an increase of absorbed doses to stomach, kidneys and bone marrow was observed, resulting in a tumor-to-organ absorbed dose ratio not significantly different with and without Entresto<jats:sup>\u00ae<\/jats:sup>.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Premedication with Entresto<jats:sup>\u00ae<\/jats:sup> results in a relevant stabilization of [<jats:sup>177<\/jats:sup>Lu]Lu-PP-FF11N and consecutively increases radiation doses in tumors and organs.<\/jats:p>\n                <jats:p><jats:italic>Trial registration<\/jats:italic> clinicaltrails.gov, NCT03647657. Registered 20 August 2018.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13550-024-01101-w","type":"journal-article","created":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T13:01:54Z","timestamp":1712408514000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In-vivo inhibition of neutral endopeptidase 1 results in higher absorbed tumor doses of [177Lu]Lu-PP-F11N in humans: the lumed phase 0b study"],"prefix":"10.1186","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03647657","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3338-9959","authenticated-orcid":false,"given":"Christof","family":"Rottenburger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hentschel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"F\u00fcrstner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"McDougall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Kottoros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalba","family":"Mansi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melpomeni","family":"Fani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Hans","family":"Vija","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Schibli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Geistlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Behe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel R.","family":"Christ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8135-5350","authenticated-orcid":false,"given":"Damian","family":"Wild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,6]]},"reference":[{"key":"1101_CR1","first-page":"1377","volume":"57","author":"JC Reubi","year":"1997","unstructured":"Reubi JC, Schaer JC, Waser B. 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Patients were recruited between December 2018 and October 2021 in a consecutive order and signed a written informed consent form in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Martin B\u00e9h\u00e9 and Roger Schibli are inventors of patent application WO 2015\/067473, which contents PP-F11N. Patent holder is Paul Scherrer Institute and the patent was licensed from 2019 to 2022 to Debiopharm International SA (Lausanne, Switzerland). No other conflict of interest relevant to this article was reported.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37"}}