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We aimed to investigate differences in therapeutic potential of the gastrin-releasing peptide receptor (GRPR) antagonists RM2 (DOTA-Pip\n 5<\/jats:sup>\n -D-Phe\n 6<\/jats:sup>\n -Gln\n 7<\/jats:sup>\n -Trp\n 8<\/jats:sup>\n -Ala\n 9<\/jats:sup>\n -Val\n 10<\/jats:sup>\n -Gly\n 11<\/jats:sup>\n -His\n 12<\/jats:sup>\n -Sta\n 13<\/jats:sup>\n -Leu\n 14<\/jats:sup>\n -NH\n 2<\/jats:sub>\n ) and AMTG (DOTA-Pip\n 5<\/jats:sup>\n -D-Phe\n 6<\/jats:sup>\n -Gln\n 7<\/jats:sup>\n -\n \u03b1<\/jats:italic>\n -Me-Trp\n 8<\/jats:sup>\n -Ala\n 9<\/jats:sup>\n -Val\n 10<\/jats:sup>\n -Gly\n 11<\/jats:sup>\n -His\n 12<\/jats:sup>\n -Sta\n 13<\/jats:sup>\n -Leu\n 14<\/jats:sup>\n -NH\n 2<\/jats:sub>\n ) radiolabeled with\n 161<\/jats:sup>\n Tb and\n 177<\/jats:sup>\n Lu in PC-3 tumor-bearing mice. We hypothesized that the superior in vivo stability of AMTG in combination with\n 161<\/jats:sup>\n Tb would result in improved tumor control and overall survival as compared to RM2 and\n 177<\/jats:sup>\n Lu counterparts.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Treatment studies in PC-3 tumor-bearing Nu\/J mice were initiated once tumor volume was\u2009~\u2009100 mm\n 3<\/jats:sup>\n .\n 161<\/jats:sup>\n Tb- and\n 177<\/jats:sup>\n Lu-Labeling was completed at 90\u00a0\u00b0C within 10\u00a0min (1.0\u00a0M sodium acetate buffer, pH\u2009=\u20095.5, molar activity of\u2009~\u200950\u00a0MBq\/nmol). Radiolabeled GRPR ligands were administered in treatment (PC-3 tumor-bearing, n\u2009=\u20096\u20137 per group) and toxicity (healthy animals, n\u2009=\u20093 per group) animals on day 0 and day 7 of the experiment (~\u200915\u00a0MBq each). Treatment animals were sacrificed once tumor volume surpassed 1,500 mm\n 3<\/jats:sup>\n . Toxicity animals were sacrificed 45 d after injection and analyzed for complete blood count and metabolic panel.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Animals were assigned to five groups (control, [\n 177<\/jats:sup>\n Lu]Lu-RM2, [\n 177<\/jats:sup>\n Lu]Lu-AMTG, [\n 161<\/jats:sup>\n Tb]Tb-RM2, [\n 161<\/jats:sup>\n Tb]Tb-AMTG). Each treatment group received a total activity amount of 26\u201331\u00a0MBq of the respective radiolabeled compound. All treatments resulted in improved tumor control and overall survival related to vehicle animals. [\n 161<\/jats:sup>\n Tb]Tb-AMTG had the longest median overall survival of 58.1\u2009\u00b1\u20095.4 d after initiation of treatment. No signs of long-term toxicity were observed during this study in any treatment group.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The combination of Auger electrons with high in vivo stability of [\n 161<\/jats:sup>\n Tb]Tb-AMTG resulted in substantially improved tumor control and overall survival in PC-3 tumor-bearing mice, thus expanding the therapeutic potential of GRPR antagonists in GRPR-expressing malignancies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s00259-026-08035-6","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:09:23Z","timestamp":1783652963000},"page":"7006-7016","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of treatment efficacy of the 161Tb- and 177Lu-Labeled GRPR antagonists AMTG and RM2 in a mouse model of prostate cancer"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7412-0297","authenticated-orcid":false,"given":"Thomas","family":"G\u00fcnther","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham S.","family":"Moses","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"G\u00fcnther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine R.","family":"Landry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stijn","family":"Ramaekers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"Van de Voorde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Ooms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Ponsard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Beinat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"8035_CR1","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.nucmedbio.2011.02.007","volume":"38","author":"S Lehenberger","year":"2011","unstructured":"Lehenberger S, Barkhausen C, Cohrs S, Fischer E, Gr\u00fcnberg J, Hohn A, et al. 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No other potential conflicts of interest relevant to this article exist.","order":1,"name":"Ethics","label":"Disclosure","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal studies were approved by the Institutional Animal Care and Use Committee at Stanford University (APLAC; # 34414). Institutional guidelines for the care and use of animals were strictly followed. Mice were housed under pathogen-free conditions. Water and food were provided ad libitum. Nu\/J mice were injected subcutaneously into the shoulder region. Tumor growth was monitored by caliper measurements. Animals were sacrificed upon reaching any of the termination criteria specified in the APLAC protocol, including but not limited to apathy, ulceration, severe weight loss, or other signs of deteriorating condition. None of these criteria applied to any animal from the experiment. This article does not contain any studies with human participants.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}