{"entity": "publication", "iuid": "e20b3bb2584c49ac80655f8a191a7eed", "timestamp": "2026-08-22T09:48:40.780Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e20b3bb2584c49ac80655f8a191a7eed.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e20b3bb2584c49ac80655f8a191a7eed"}}, "title": "Preclinical Characterization of a Stabilized Gastrin-Releasing Peptide Receptor Antagonist for Targeted Cancer Theranostics.", "authors": [{"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P"}, {"family": "Gorislav", "given": "Alisa", "initials": "A"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Maina", "given": "Theodosia", "initials": "T", "orcid": "0000-0002-1123-2486", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b43f747494e64e9cacf77979cdbaf0a6.json"}}, {"family": "Nock", "given": "Berthold A", "initials": "BA", "orcid": "0000-0002-6028-9112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/58c006b61c854f2f8e61b2ddb0d21096.json"}}, {"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": "2023-07-14", "journal": {"title": "Biomolecules", "issn": "2218-273X", "volume": "13", "issue": "7", "issn-l": null}, "abstract": "Radiolabeled gastrin-releasing peptide receptor (GRPR) antagonists have shown great promise for the theranostics of prostate cancer; however, their suboptimal metabolic stability leaves room for improvements. It was recently shown that the replacement of Gly11 with Sar11 in the peptidic [D-Phe6,Leu13-NHEt,des-Met14]BBN(6-14) chain stabilized the [99mTc]Tc-DB15 radiotracer against neprilysin (NEP). We herein present DOTAGA-PEG2-(Sar11)RM26 (AU-RM26-M1), after Gly11 to Sar11-replacement. The impact of this replacement on the metabolic stability and overall biological performance of [111In]In-AU-RM26-M1 was studied using a head-to-head comparison with the unmodified reference [111In]In-DOTAGA-PEG2-RM26. In vitro, the cell uptake of [111In]In-AU-RM26-M1 could be significantly reduced in the presence of a high-excess GRPR-blocker that demonstrated its specificity. The cell uptake of both radiolabeled GRPR antagonists increased with time and was superior for [111In]In-AU-RM26-M1. The dissociation constant reflected strong affinities for GRPR (500 pM for [111In]In-AU-RM26-M1). [111In]In-AU-RM26-M1 showed significantly higher stability in peripheral mice blood at 5 min pi (88 \u00b1 8% intact) than unmodified [111In]In-DOTAGA-PEG2-RM26 (69 \u00b1 2% intact; p < 0.0001). The administration of a NEP inhibitor had no significant impact on the Sar11-compound (91 \u00b1 2% intact; p > 0.05). In vivo, [111In]In-AU-RM26-M1 showed high and GRPR-mediated uptake in the PC-3 tumors (7.0 \u00b1 0.7%IA/g vs. 0.9 \u00b1 0.6%IA/g in blocked mice) and pancreas (2.2 \u00b1 0.6%IA/g vs. 0.3 \u00b1 0.2%IA/g in blocked mice) at 1 h pi, with rapid clearance from healthy tissues. The tumor uptake of [111In]In-AU-RM26-M1 was higher than for [111In]In-DOTAGA-PEG2-RM26 (at 4 h pi, 5.7 \u00b1 1.8%IA/g vs. 3 \u00b1 1%IA/g), concordant with its higher stability. The implanted PC-3 tumors were visualized with high contrast in mice using [111In]In-AU-RM26-M1 SPECT/CT. The Gly11 to Sar11-substitution stabilized [111In]In-DOTAGA-PEG2-(Sar11)RM26 against NEP without negatively affecting other important biological features. These results support the further evaluation of AU-RM26-M1 for prostate cancer theranostics after labeling with clinically relevant radionuclides.", "doi": "10.3390/biom13071134", "pmid": "37509170", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10377574"}, {"db": "pii", "key": "biom13071134"}], "notes": [], "created": "2026-08-21T13:01:09.556Z", "modified": "2026-08-21T13:01:09.759Z"}