{"entity": "publication", "iuid": "612efa2811274e2596fcccfca71c1d4c", "timestamp": "2026-08-22T08:30:15.181Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/612efa2811274e2596fcccfca71c1d4c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/612efa2811274e2596fcccfca71c1d4c"}}, "title": "Evaluation of ABD-Linked RM26 Conjugates for GRPR-Targeted Drug Delivery.", "authors": [{"family": "Nagy", "given": "\u00c1bel", "initials": "\u00c1"}, {"family": "Abouzayed", "given": "Ayman", "initials": "A"}, {"family": "Kanellopoulos", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-0617-3936", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/85ce3df2ffae4754946f11bb2e98ef97.json"}}, {"family": "Landmark", "given": "Fredrika", "initials": "F"}, {"family": "Bezverkhniaia", "given": "Ekaterina", "initials": "E"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}, {"family": "Eriksson Karlstr\u00f6m", "given": "Amelie", "initials": "A", "orcid": "0000-0002-0695-5188", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/084ac56a883542f0b79ac6f63a9d6b1d.json"}}], "type": "journal article", "published": "2024-08-27", "journal": {"title": "ACS Omega", "issn": "2470-1343", "volume": "9", "issue": "34", "pages": "36122-36133", "issn-l": "2470-1343"}, "abstract": "Targeting the gastrin-releasing peptide receptor (GRPR) with the bombesin analogue RM26, a 9 aa peptide, has been a promising strategy for cancer theranostics, with recent success in radionuclide imaging of prostate cancer. However, therapeutic application of the short peptide RM26 would require a longer half-life to prevent fast clearance from the circulation. Conjugation to an albumin-binding domain (ABD) is a viable strategy to extend the in vivo half-life of peptides and proteins. We previously reported an ABD-fused RM26 peptide targeting GRPR (ABD-RM26 Gen 1) that showed prolonged and stable tumor uptake over 144 h; however, the observed high kidney uptake indicated that the conjugate's binding to albumin was reduced and that this could be an obstacle for its use as a delivery system for targeted therapy, especially for radiotherapy. Here, we have designed, produced, and preclinically evaluated a series of novel ABD-RM26 conjugates with the aim of improving the conjugate's binding to albumin and decreasing the kidney uptake. We developed three second-generation constructs with varying formats, differing in the relative positions of the targeting moieties and the radionuclide chelator. The produced conjugates were radiolabeled with indium-111 and evaluated in vitro and in vivo. All constructs displayed improved biophysical characteristics, biodistribution, and lower kidney uptake compared to previously reported first-generation molecules. The ABD-RM26 Gen 2A conjugate showed the best biodistribution profile with a nearly 6-fold reduction in kidney uptake. However, the ABD-RM26 Gen 2A conjugate's binding to GRPR was compromised. This conjugate's assembly of albumin- and GRPR-binding moieties might be used for further development of drug conjugates for targeted therapy/radiotherapy of GRPR-expressing cancers.", "doi": "10.1021/acsomega.4c00489", "pmid": "39220525", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11359615"}], "notes": [], "created": "2026-08-21T11:36:49.821Z", "modified": "2026-08-21T11:36:49.966Z"}