{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:01:08Z","timestamp":1784037668476,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"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-180300"],"award-info":[{"award-number":["PJT-180300"]}]},{"name":"Canadian Institutes of Health Research","award":["PJT-183956"],"award-info":[{"award-number":["PJT-183956"]}]},{"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-180300"],"award-info":[{"award-number":["PJT-180300"]}]},{"name":"China Scholarship Council","award":["PJT-183956"],"award-info":[{"award-number":["PJT-183956"]}]},{"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: Overexpressed in various solid tumors, the gastrin-releasing peptide receptor (GRPR) is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake of the current clinically evaluated GRPR-targeted radiopharmaceuticals limits their applications. In this study, we replaced the Pro14 residue in our previously reported GRPR-targeted LW02056 and ProBOMB5 with 4,4-difluoroproline (diF-Pro) to obtain an agonist LW02060 (DOTA-Pip-[D-Phe6,Tle10,NMe-His12,diF-Pro14]Bombesin(6\u201314)) and an antagonist LW02080 (DOTA-Pip-[D-Phe6,NMe-Gly11,Leu13(\u03c8)diF-Pro14]Bombesin(6\u201314)), respectively. Methods\/Results: The binding affinities (Ki) of Ga-LW02060, Ga-LW02080, Lu-LW02060, and Lu-LW02080 were measured by in vitro competition binding assays using PC-3 cells and were found to be 5.57 \u00b1 2.47, 21.7 \u00b1 6.69, 8.00 \u00b1 2.61, and 32.1 \u00b1 8.14 nM, respectively. The 68Ga- and 177Lu-labeled ligands were obtained in 36\u201375% decay-corrected radiochemical yields with &gt;95% radiochemical purity. PET imaging, SPECT imaging, and ex vivo biodistribution studies were conducted in PC-3 tumor-bearing mice. Both [68Ga]Ga-LW02060 and [68Ga]Ga-LW02080 enabled clear tumor visualization in PET images at 1 h post-injection (pi). Tumor uptake values of [68Ga]Ga-LW02060 and [68Ga]Ga-LW02080 at 1 h pi were 16.8 \u00b1 2.70 and 7.36 \u00b1 1.33 %ID\/g, respectively, while their pancreas uptake values were 3.12 \u00b1 0.89 and 0.38 \u00b1 0.04 %ID\/g, respectively. Compared to [177Lu]Lu-LW02080, [177Lu]Lu-LW02060 showed higher tumor uptake at all time points (1, 4, 24, 72, and 120 h pi). However, fast tumor clearance was observed for both [177Lu]Lu-LW02060 and [177Lu]Lu-LW02080. Conclusions: Our data demonstrate that [68Ga]Ga-LW02060 is promising for clinical translation for the detection of GRPR-expressing tumor lesions. However, further optimizations are needed for [177Lu]Lu-LW02060 and [177Lu]Lu-LW02080 to prolong tumor retention for therapeutic applications.<\/jats:p>","DOI":"10.3390\/ph18020234","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T05:53:22Z","timestamp":1739166802000},"page":"234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis and Evaluation of 68Ga- and 177Lu-Labeled [diF-Pro14]Bombesin(6\u221214) Analogs for Detection and Radioligand Therapy of 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":"Chao-Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon","family":"Chapple","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\/0000-0003-4617-9248","authenticated-orcid":false,"given":"Antonio A. W. L.","family":"Wong","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":"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"}]},{"given":"Carlos F.","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":[[2025,2,8]]},"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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