{"entity": "publication", "iuid": "b4ed80b42ea84aa7b96fcdf6031bb19a", "timestamp": "2026-09-28T11:16:24.885Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b4ed80b42ea84aa7b96fcdf6031bb19a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b4ed80b42ea84aa7b96fcdf6031bb19a"}}, "title": "Preclinical evaluation of new GRPR-antagonists with improved metabolic stability for radiotheranostic use in oncology.", "authors": [{"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P"}, {"family": "Mattsson", "given": "Adam", "initials": "A"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Obeid", "given": "Karim", "initials": "K"}, {"family": "Nock", "given": "Berthold A", "initials": "BA"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}, {"family": "Maina", "given": "Theodosia", "initials": "T"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}], "type": "journal article", "published": "2024-02-16", "journal": {"title": "EJNMMI Radiopharm Chem", "issn": "2365-421X", "volume": "9", "issue": "1", "pages": "13", "issn-l": null}, "abstract": "The gastrin-releasing peptide receptor (GRPR) has been extensively studied as a biomolecular target for peptide-based radiotheranostics. However, the lack of metabolic stability and the rapid clearance of peptide radioligands, including radiolabeled GRPR-antagonists, often impede clinical application. Aiming at circumventing these drawbacks, we have designed three new GRPR-antagonist radioligands using [99mTc]Tc-DB15 ([99mTc]Tc-N4-AMA-DIG-DPhe-Gln-Trp-Ala-Val-Sar-His-Leu-NHEt; AMA: p-aminomethylaniline; DIG: diglycolate) as a motif, due to its high GRPR-affinity and stability to neprilysin (NEP). The new analogues carry the DOTAGA-chelator (1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid) through different linkers at the N-terminus to allow for labeling with the theranostic radionuclide pair In-111/Lu-177. After labeling with In-111 the following radioligands were evaluated: (i) [111In]In-AU-SAR-M1 ([111In]In-DOTAGA-AMA-DIG-DPhe-Gln-Trp-Ala-Val-Sar-His-Leu-NHEt), (ii) [111In]In-AU-SAR-M2 ([111In]In-[DOTAGA-Arg]AU-SAR-M1) and (iii) [111In]In-AU-SAR-M3 ([111In]In-[DOTAGA-DArg]AU-SAR-M1).\n\nThese radioligands were compared in a series of in vitro assays using prostate adenocarcinoma PC-3 cells and in murine models. They all displayed high and GRPR-specific uptake in PC-3 cells. Analysis of mice blood collected 5 min post-injection (pi) revealed similar or even higher metabolic stability of the new radioligands compared with [99mTc]Tc-DB15. The stability could be further increased when the mice were treated with Entresto\u00ae to in situ induce NEP-inhibition. In PC-3 xenograft-bearing mice, [111In]In-AU-SAR-M1 displayed the most favourable biodistribution profile, combining a good tumor retention with the highest tumor-to-organ ratios, with the kidneys as the dose-limiting organ.\n\nThese findings strongly point at AU-SAR-M1 as a promising radiotherapeutic candidate when labeled with Lu-177, or other medically appealing therapeutic radiometals, especially when combined with in situ NEP-inhibition. To this goal further investigations are currently pursued.", "doi": "10.1186/s41181-024-00242-6", "pmid": "38366299", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10873254"}, {"db": "pii", "key": "10.1186/s41181-024-00242-6"}], "notes": [], "created": "2026-09-23T12:16:31.411Z", "modified": "2026-09-23T12:16:31.462Z"}