{"entity": "publication", "iuid": "7f458e1ae1cf4a4e890131c1ba71511e", "timestamp": "2026-08-20T20:48:41.902Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/7f458e1ae1cf4a4e890131c1ba71511e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/7f458e1ae1cf4a4e890131c1ba71511e"}}, "title": "Trastuzumab cotreatment improves survival of mice with PC-3 prostate cancer xenografts treated with the GRPR antagonist 177 Lu-DOTAGA-PEG2 -RM26.", "authors": [{"family": "Mitran", "given": "Bogdan", "initials": "B"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Konijnenberg", "given": "Mark W", "initials": "MW"}, {"family": "Maina", "given": "Theodosia", "initials": "T"}, {"family": "Nock", "given": "Berthold A", "initials": "BA"}, {"family": "Altai", "given": "Mohamed", "initials": "M"}, {"family": "Vorobyeva", "given": "Anzhelika", "initials": "A"}, {"family": "Larhed", "given": "Mats", "initials": "M"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V"}, {"family": "de Jong", "given": "Marion", "initials": "M"}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U"}, {"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": "2019-12-15", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "145", "issue": "12", "pages": "3347-3358", "issn-l": "0020-7136"}, "abstract": "Gastrin-releasing peptide receptors (GRPRs) are overexpressed in prostate cancer and are suitable for targeted radionuclide therapy (TRT). We optimized the bombesin-derived GRPR-antagonist PEG2 -RM26 for labeling with 177 Lu and further determined the effect of treatment with 177 Lu-labeled peptide alone or in combination with the anti-HER2 antibody trastuzumab in a murine model. The PEG2 -RM26 analog was coupled to NOTA, NODAGA, DOTA and DOTAGA chelators. The peptide-chelator conjugates were labeled with 177 Lu and characterized in vitro and in vivo. A preclinical therapeutic study was performed in PC-3 xenografted mice. Mice were treated with intravenous injections (6 cycles) of (A) PBS, (B) DOTAGA-PEG2 -RM26, (C) 177 Lu-DOTAGA-PEG2 -RM26, (D) trastuzumab or (E) 177 Lu-DOTAGA-PEG2 -RM26 in combination with trastuzumab. 177 Lu-DOTAGA-PEG2 -RM26 demonstrated quantitative labeling yield at high molar activity (450 GBq/\u03bcmol), high in vivo stability (5 min pi >98% of radioligand remained when coinjected with phosphoramidon), high affinity to GRPR (KD = 0.4 \u00b1 0.2 nM), and favorable biodistribution (1 hr pi tumor uptake was higher than in healthy tissues, including the kidneys). Therapy with 177 Lu-DOTAGA-PEG2 -RM26 induced a significant inhibition of tumor growth. The median survival for control groups was significantly shorter than for treated groups (Group C 66 days, Group E 74 days). Trastuzumab together with radionuclide therapy significantly improved survival. No treatment-related toxicity was observed. In conclusion, based on in vitro and in vivo characterization of the four 177 Lu-labeled PEG2 -RM26 analogs, we concluded that 177 Lu-DOTAGA-PEG2 -RM26 was the most promising analog for TRT. Radiotherapy using 177 Lu-DOTAGA-PEG2 -RM26 effectively inhibited tumor growth in vivo in a murine prostate cancer model. Anti-HER2 therapy additionally improved survival.", "doi": "10.1002/ijc.32401", "pmid": "31077356", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6852655"}], "notes": [], "created": "2026-08-20T06:33:36.972Z", "modified": "2026-08-20T06:33:37.052Z"}