{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:24:17Z","timestamp":1791588257190,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T00:00:00Z","timestamp":1742688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research","award":["PJT-162243"],"award-info":[{"award-number":["PJT-162243"]}]},{"name":"Canadian Institutes of Health Research","award":["PJT-180299"],"award-info":[{"award-number":["PJT-180299"]}]},{"name":"Canadian Institutes of Health Research","award":["PJT-180300"],"award-info":[{"award-number":["PJT-180300"]}]},{"name":"Canadian Institutes of Health Research","award":["202008310216"],"award-info":[{"award-number":["202008310216"]}]},{"name":"China Scholarship Council","award":["PJT-162243"],"award-info":[{"award-number":["PJT-162243"]}]},{"name":"China Scholarship Council","award":["PJT-180299"],"award-info":[{"award-number":["PJT-180299"]}]},{"name":"China Scholarship Council","award":["PJT-180300"],"award-info":[{"award-number":["PJT-180300"]}]},{"name":"China Scholarship Council","award":["202008310216"],"award-info":[{"award-number":["202008310216"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Gastrin-releasing peptide receptor is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake of reported GRPR-targeted radioligands limits their clinical applications. Our group previously reported one 68Ga-labeled GRPR antagonist, [68Ga]Ga-TacsBOMB5 (68Ga-DOTA-Pip-[D-Phe6,NMe-Gly11,Leu13\u03c8Thz14]Bombesin(6\u201314)), and two agonists, [68Ga]Ga-LW01110 (68Ga-DOTA-Pip-[D-Phe6,Tle10,NMe-His12,Thz14]Bombesin(6\u201314)) and [68Ga]Ga-LW01142 (68Ga-DOTA-Pip-[D-Phe6,His7,Tle10,NMe-His12,Thz14]Bombesin(6\u201314)) showing minimal pancreas uptake. Thus, in this study, we prepared their 177Lu-labeled analogs, evaluated their therapeutic potentials, and compared them with the clinically evaluated [177Lu]Lu-AMBA. Methods: GRPR binding affinities were determined by in vitro competition binding assay using PC-3 prostate cancer cells. Longitudinal SPECT\/CT imaging and ex vivo biodistribution studies were conducted in PC-3 tumor-bearing mice. Dosimetry data were calculated from the biodistribution results. Results: The Ki(GRPR) values of Lu-TacsBOMB5, Lu-LW01110, Lu-LW01142, and Lu-AMBA were 12.6 \u00b1 1.02, 3.07 \u00b1 0.15, 2.37 \u00b1 0.28, and 0.33 \u00b1 0.16 nM, respectively. SPECT\/CT images and biodistribution results demonstrated good tumor accumulation of [177Lu]Lu-TacsBOMB5, [177Lu]Lu-LW01110, and [177Lu]Lu-LW01142 at early time points with rapid clearance over time. The pancreas uptake of all three [Thz14]Bombesin(6\u201314)-derived ligands was significantly lower than that of [177Lu]Lu-AMBA at all time points. The calculated absorbed doses of [177Lu]Lu-TacsBOMB5, [177Lu]Lu-LW01110, and [177Lu]Lu-LW01142 in PC-3 tumor xenografts were 87.1, 312, and 312 mGy\/MBq, respectively, higher than that of [177Lu]Lu-AMBA (79.1 mGy\/MBq), but lower than that of the previously reported [177Lu]Lu-RM2 (429 mGy\/MBq). Conclusions: Our data suggest that [177Lu]Lu-TacsBOMB5 and [177Lu]Lu-LW01142 reduce radiation exposure to the pancreas. However, further optimizations are needed for both radioligands to prolong their tumor retention and enhance treatment efficacy.<\/jats:p>","DOI":"10.3390\/ph18040449","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T13:48:20Z","timestamp":1742824100000},"page":"449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel 177Lu-Labeled [Thz14]Bombesin(6\u201314) Derivatives with Low Pancreas Accumulation for Targeting Gastrin-Releasing Peptide Receptor-Expressing Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon E.","family":"Chapple","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiou-Ting","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Kurkowska","sequence":"additional","affiliation":[{"name":"Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"},{"name":"Department of Nuclear Medicine, Pomeranian Medical University, 70-204 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan P.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing Sum","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5345-0031","authenticated-orcid":false,"given":"Pauline","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Uribe","sequence":"additional","affiliation":[{"name":"Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"},{"name":"Department of Molecular Imaging and Therapy, BC Cancer, Vancouver, BC V5Z 4E6, Canada"},{"name":"Department of Radiology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7995-3581","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"B\u00e9nard","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"},{"name":"Department of Molecular Imaging and Therapy, BC Cancer, Vancouver, BC V5Z 4E6, Canada"},{"name":"Department of Radiology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0739-0780","authenticated-orcid":false,"given":"Kuo-Shyan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"},{"name":"Department of Molecular Imaging and Therapy, BC Cancer, Vancouver, BC V5Z 4E6, Canada"},{"name":"Department of Radiology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/pr.107.07108","article-title":"International Union of Pharmacology. 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