{"entity": "researcher", "timestamp": "2026-08-22T09:49:25.510Z", "family": "Nock", "given": "Berthold A", "initials": "BA", "orcid": "0000-0002-6028-9112", "affiliations": ["Molecular Radiopharmacy, INRaSTES, NCSR \"Demokritos\", 15310 Athens, Greece."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/58c006b61c854f2f8e61b2ddb0d21096.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/58c006b61c854f2f8e61b2ddb0d21096"}}, "publications": [{"entity": "publication", "iuid": "9f6b8e882b61420687b18816fd59c8fe", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9f6b8e882b61420687b18816fd59c8fe.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9f6b8e882b61420687b18816fd59c8fe"}}, "title": "GRPR-Antagonists Carrying DOTAGA-Chelator via Positively Charged Linkers: Perspectives for Prostate Cancer Theranostics.", "authors": [{"family": "Obeid", "given": "Karim", "initials": "K"}, {"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-0617-3936", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97.json"}}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Mattsson", "given": "Adam", "initials": "A"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "Nock", "given": "Berthold A", "initials": "BA", "orcid": "0000-0002-6028-9112", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/58c006b61c854f2f8e61b2ddb0d21096.json"}}, {"family": "Maina", "given": "Theodosia", "initials": "T", "orcid": "0000-0002-1123-2486", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b43f747494e64e9cacf77979cdbaf0a6.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": "2024-04-08", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "16", "issue": "4", "issn-l": null}, "abstract": "Gastrin-releasing peptide receptor (GRPR)-antagonists have served as motifs in the development of theranostic radioligands for prostate cancer. Our efforts have been focused on the development of radiolabeled RM26 (H-DPhe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Sta13-Leu14-NH2) analogs, such as [111In]In-DOTAGA-PEG2-RM26. We recently showed that its Gly11/Sar11-substituted version, [111In]In-AU-RM26-M1, resisted degradation by neprilysin (NEP) while in circulation and achieved higher tumor uptake in mice. We herein introduce the following three new AU-RM26-M1 mimics labeled with In-111, with basic residues in the linker: (i) AU-RM26-M2 (PEG2-Pip), (ii) AU-RM26-M3 (PEG2-Arg), and (iii) AU-RM26-M4 (Arg-Arg-Pip). These analogs were compared in PC-3 cells and animal models vs. AU-RM26-M1 (reference). The new analogs showed high affinity and specificity for the GRPR, exhibiting an uptake and distribution pattern in PC-3 cells typical for a radiolabeled GRPR-antagonist. They showed high stability in peripheral mice blood, except for [111In]In-AU-RM26-M3. AU-RM26-M4 achieved the highest tumor uptake and promising background clearance, followed by [111In]In-RM26-M2, showing lower background levels. These findings were confirmed for [111In]In-AU-RM26-M2 and [111In]In-AU-RM26-M4 by micro-SPECT/CT at 4 and 24 h post-injection. Hence, the type of positively charged residues in the linker of AU-RM26-M1 mimics strongly influenced biological behavior. The analogs with Pip next to DPhe6 demonstrated the best overall characteristics and warrant further investigation.", "doi": "10.3390/pharmaceutics16040513", "pmid": "38675174", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11054746"}, {"db": "pii", "key": "pharmaceutics16040513"}], "notes": [], "created": "2026-08-21T13:05:03.776Z", "modified": "2026-08-21T13:05:03.852Z"}, {"entity": "publication", "iuid": "e20b3bb2584c49ac80655f8a191a7eed", "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"}]}