{"entity": "publication", "iuid": "64bfcf06d3d845d88ba95629eb9525a2", "timestamp": "2026-08-23T09:24:54.043Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/64bfcf06d3d845d88ba95629eb9525a2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/64bfcf06d3d845d88ba95629eb9525a2"}}, "title": "Gastrin-releasing peptide receptor as theranostic target in estrogen-receptor positive breast cancer: A preclinical study of the theranostic pair [55Co]Co- and [177Lu]Lu-DOTA-RM26.", "authors": [{"family": "Baun", "given": "Christina", "initials": "C"}, {"family": "Olsen", "given": "Birgitte Brinkmann", "initials": "BB"}, {"family": "Alves", "given": "Carla Maria Lourenco", "initials": "CML"}, {"family": "Ditzel", "given": "Henrik J\u00f8rn", "initials": "HJ"}, {"family": "Terp", "given": "Mikkel", "initials": "M"}, {"family": "Hildebrandt", "given": "Malene Grubbe", "initials": "MG"}, {"family": "Poulsen", "given": "Charlotte Aaberg", "initials": "CA"}, {"family": "G\u00e9", "given": "Lorraine Gaenaelle", "initials": "LG"}, {"family": "Gammelsr\u00f8d", "given": "Vigga Sand", "initials": "VS"}, {"family": "Orlova", "given": "Anna", "initials": "A"}, {"family": "Dam", "given": "Johan Hygum", "initials": "JH"}, {"family": "Thisgaard", "given": "Helge", "initials": "H"}], "type": "journal article", "published": "2024-09-25", "journal": {"title": "Nucl. Med. Biol.", "issn": "1872-9614", "volume": "138-139", "pages": "108961", "issn-l": "0969-8051"}, "abstract": "Patients with advanced metastatic estrogen receptor-positive breast cancer often develop resistance to standard treatments, leading to uncontrolled progression. Thus, innovative therapies are urgently needed. The gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers, including breast cancer, making it an interesting theranostic target. RM26, a GRPR-targeting antagonist, has demonstrated promising in vivo kinetics in prostate cancer models. This study evaluated the theranostic capabilities of [55Co]Co-/[177Lu]Lu-DOTA-RM26 in vitro in estrogen receptor-positive breast cancer cells and assessed the diagnostic potential of [55Co]Co-DOTA-RM26 in vivo in a breast cancer mouse model.\n\nWe analyzed the binding specificity of [57Co]Co-/[177Lu]Lu-DOTA-RM26 in T47D breast cancer cells, using [57Co]Co-DOTA-RM26 as a surrogate for [55Co]Co-DOTA-RM26. The therapeutic efficacy of increasing [177Lu]Lu-DOTA-RM26 concentrations was determined via viability assay in vitro. Ex vivo biodistribution of [57Co]Co-DOTA-RM26 (17.2 \u00b1 2.7 kBq, 33 \u00b1 5.2 pmol/mouse) was investigated in 12 mice (n= 4/group) with orthotopic breast cancer tumors. The mice were sacrificed at 4 and 24 h post-injection (pi), including a blocking group (20 nmol of unlabeled [Tyr4]-Bombesin) at 4 h pi. For imaging, two tumor-bearing mice underwent [55Co]Co-DOTA-RM26 PET/CT, 4 and 24 h pi (2.8 \u00b1 0.2 MBq, 167.5 \u00b1 0.5 pmol/mouse), with or without GRPR blocking.\n\nIn vitro studies revealed high, specific binding of [57Co]Co-DOTA-RM26 (43 \u00b1 1 % of total added activity per 106 cells (%IA/106)) and [177Lu]Lu-DOTA-RM26 (37 \u00b1 4 %IA/106). The activity was predominantly localized at the cell surface: 71 \u00b1 3 % and 80 \u00b1 6 % for [57Co]Co-DOTA-RM26 and [177Lu]Lu-DOTA-RM26, respectively. [177Lu]Lu-DOTA-RM26 significantly reduced cell viability at all activity concentrations >0.625 MBq/mL (p < 0.0001), with cell viability below 1 % at concentrations \u22655 MBq/mL. Biodistribution data (n = 12) indicated a high, specific tumor uptake of [57Co]Co-DOTA-RM26, surpassing all other tissues significantly at both time points, 3.7 \u00b1 0.6 % of the injected activity per gram (%IA/g) 4 h pi and 0.98 \u00b1 0.05 %IA/g 24 h pi. The kidneys showed the second-highest uptake (2.0 \u00b1 0.1 %IA/g 4 h pi), followed by the pancreas (1.4 \u00b1 0.4 %IA/g 4 h pi). PET/CT imaging with [55Co]Co-DOTA-RM26 supported the biodistribution data and, distinctly visualized the tumor 24 h pi and showed an improved tumor-to-background compared to the earlier time points. Effective GRPR blocking significantly reduced tumor uptake in the PET images 24 h pi.\n\nThese findings suggest that the theranostic pair [55Co]Co-/[177Lu]Lu-DOTA-RM26 holds significant promise as a theranostic agent for estrogen receptor-positive breast cancer.", "doi": "10.1016/j.nucmedbio.2024.108961", "pmid": "39357076", "labels": [], "xrefs": [{"db": "pii", "key": "S0969-8051(24)00087-8"}], "notes": [], "created": "2026-08-21T11:26:54.891Z", "modified": "2026-08-21T11:26:54.925Z"}