{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:36:40Z","timestamp":1789763800814,"version":"4.0.1"},"reference-count":67,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Movember Discovery Grant from Prostate Cancer Canada","award":["D2014-15"],"award-info":[{"award-number":["D2014-15"]}]},{"name":"Movember Discovery Grant from Prostate Cancer Canada","award":["MOP-166037"],"award-info":[{"award-number":["MOP-166037"]}]},{"name":"Canadian Institutes of Health Research","award":["D2014-15"],"award-info":[{"award-number":["D2014-15"]}]},{"name":"Canadian Institutes of Health Research","award":["MOP-166037"],"award-info":[{"award-number":["MOP-166037"]}]},{"name":"Fonds de Recherche du Qu\u00e9bec Sant\u00e9 (FRQS)-funded Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CRCHUS)","award":["D2014-15"],"award-info":[{"award-number":["D2014-15"]}]},{"name":"Fonds de Recherche du Qu\u00e9bec Sant\u00e9 (FRQS)-funded Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke (CRCHUS)","award":["MOP-166037"],"award-info":[{"award-number":["MOP-166037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: This study explores the potential of the inducible G protein-coupled kinin B1 receptor (B1R) as a target for the diagnosis and treatment of prostate cancer (PCa) and aims to develop the first theranostic agent targeting hB1R for both molecular imaging and radionuclide therapy. Methods: B1R expression was analyzed via qPCR and immunohistochemistry in human PCa cells and tissues specimens. A novel 64Cu\/NOTA-conjugated peptide analog of the potent B1R antagonist R954 was synthetized and evaluated in vitro and in vivo. Results: B1R was confirmed to be expressed (RNA, protein) by varying degrees in all PCa cell lines and tissues investigated, with protein level significantly correlating with tumor grades. This finding was supported by similar analyses from the TCGA and MSKCC databases. In vitro, the 64Cu\/NOTA-\u03b2Ala-R954 conjugate showed nanomolar affinity\/potency at hB1R, complete plasma stability over 24 h, significant cellular uptake (up to 33% of ID at 24 h), and dose-dependent anti-clonal growth effects. In vivo, the radioconjugate remained stable in circulation for up to 90 min and was primarily excreted intact via the kidneys following IV administration. Intravenous 64Cu\/NOTA-\u03b2Ala-R954 (7.5 MBq) effectively detected subcutaneous PCa xenografts via \u00b5PET imaging in male athymic nude mice. At a single higher dose (65 MBq; 50 \u00b5g\/kg), it significantly reduced tumor growth without observable toxicity. This antitumor effect was associated with increased apoptosis (active caspase-3) and reduced proliferation (Ki67), as shown by immunohistochemistry. In contrast, the nonradioactive NatCu\/NOTA-\u03b2Ala-R954 had no therapeutic effect at the same dose. Conclusions: Our findings provide proof-of-concept for the potential theranostic use of 64Cu\/NOTA-R954 in PCa, and potentially other types of B1R-positive solid cancers.<\/jats:p>","DOI":"10.3390\/pharmaceutics17091215","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T14:45:46Z","timestamp":1758206746000},"page":"1215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Theranostic Potential of a New 64Cu-Labeled NOTA-R954 Peptide Conjugate for Kinin B1R Expressing Prostate Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Sadaf","family":"Ghanaatgar Kasbi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Institute of Pharmacology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Savard","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Institute of Pharmacology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7785-5881","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Couture","sequence":"additional","affiliation":[{"name":"TransBIOTech, L\u00e9vis, QC G6V 6Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9l\u00e9na","family":"Dubuc","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Institute of Pharmacology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Dumulon-Perreault","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0936-6618","authenticated-orcid":false,"given":"Marie-Edith","family":"Nepveu-Traversy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Institute of Pharmacology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia","family":"Ait-Mohand","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sabbagh","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Urology, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh","family":"Geha","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-4512","authenticated-orcid":false,"given":"Brigitte","family":"Gu\u00e9rin","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-1589","authenticated-orcid":false,"given":"Yves","family":"Dory","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernand","family":"Gobeil","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"},{"name":"Institute of Pharmacology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","unstructured":"(2024, March 10). Canadian Cancer Society: Prostate Cancer Statistics. Available online: https:\/\/cancer.ca\/en\/cancer-information\/cancer-types\/prostate\/statistics."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"413","DOI":"10.21037\/tau.2017.03.53","article-title":"Positron emission tomography (PET) in primary prostate cancer staging and risk assessment","volume":"6","author":"Bednarova","year":"2017","journal-title":"Transl. Androl. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kania, E., Janica, M., Nesterowicz, M., Modzelewski, W., Cybulski, M., and Janica, J. (2025). Advances and Challenges in Prostate Cancer Diagnosis: A Comprehensive Review. Cancers, 17.","DOI":"10.3390\/cancers17132137"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.euros.2025.03.006","article-title":"Personalised Prostate Cancer Diagnosis: Evaluating Biomarker-based Approaches to Reduce Unnecessary Magnetic Resonance Imaging and Biopsy Procedures","volume":"75","author":"Soeterik","year":"2025","journal-title":"Eur. Urol. Open Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41571-022-00652-y","article-title":"Radiotheranostics in oncology: Current challenges and emerging opportunities","volume":"19","author":"Bodei","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.4103\/0975-7406.137249","article-title":"Theranostics: A treasured tailor for tomorrow","volume":"6","author":"Jeelani","year":"2014","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrc2069","article-title":"G-protein-coupled receptors and cancer","volume":"7","author":"Dorsam","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"481","DOI":"10.7150\/thno.4024","article-title":"Radiolabeled peptides: Valuable tools for the detection and treatment of cancer","volume":"2","author":"Fani","year":"2012","journal-title":"Theranostics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nrd3320","article-title":"G protein-coupled receptors: Novel targets for drug discovery in cancer","volume":"10","author":"Lappano","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"118206","DOI":"10.1016\/j.lfs.2020.118206","article-title":"Application of radiolabeled peptides in tumor imaging and therapy","volume":"258","author":"Mohtavinejad","year":"2020","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"762","DOI":"10.2967\/jnumed.112.112169","article-title":"Targeted radiotherapy of prostate cancer with a gastrin-releasing peptide receptor antagonist is effective as monotherapy and in combination with rapamycin","volume":"54","author":"Dumont","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1007\/s00259-015-3232-1","article-title":"Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [68Ga]SB3 and PET\/CT","volume":"43","author":"Maina","year":"2016","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2967\/jnumed.116.178889","article-title":"Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results","volume":"58","author":"Nock","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.urology.2015.10.012","article-title":"VPAC1 Targeted 64Cu-TP3805 Positron Emission Tomography Imaging of Prostate Cancer: Preliminary Evaluation in Man","volume":"88","author":"Tripathi","year":"2016","journal-title":"Urology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"412","DOI":"10.7150\/thno.7324","article-title":"Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist--from mice to men","volume":"4","author":"Wieser","year":"2014","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, X., Cai, H., Wu, X., Li, L., Wu, H., and Tian, R. (2020). New frontiers in molecular imaging using peptide-based radiopharmaceuticals for prostate cancer. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.583309"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.canlet.2013.12.009","article-title":"The role of kinin receptors in cancer and therapeutic opportunities","volume":"345","author":"Sirois","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1517\/14728222.2012.662957","article-title":"Kinin receptors as targets for cancer therapy","volume":"16","author":"Figueroa","year":"2012","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.intimp.2007.06.006","article-title":"Structural modification of the highly potent peptide bradykinin B1 receptor antagonist B9958","volume":"8","author":"Gera","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8140","DOI":"10.1073\/pnas.120035997","article-title":"Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors","volume":"97","author":"Pesquero","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","first-page":"2037","article-title":"Bradykinin receptor subtype 1 expression and function in prostate cancer","volume":"63","author":"Taub","year":"2003","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.peptides.2013.12.009","article-title":"Preclinical pharmacology, metabolic stability, pharmacokinetics and toxicology of the peptidic kinin B1 receptor antagonist R-954","volume":"52","author":"Gobeil","year":"2014","journal-title":"Peptides"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1139\/y02-053","article-title":"Kinin B1 receptor antagonists with multi-enzymatic resistance properties","volume":"80","author":"Neugebauer","year":"2002","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1161\/01.HYP.33.3.823","article-title":"Kinin B1 receptor antagonists containing alpha-methyl-L-phenylalanine: In vitro and in vivo antagonistic activities","volume":"33","author":"Gobeil","year":"1999","journal-title":"Hypertension"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1161\/01.HYP.28.5.833","article-title":"Structure-activity studies of B1 receptor-related peptides. Antagonists","volume":"28","author":"Gobeil","year":"1996","journal-title":"Hypertension"},{"key":"ref_27","first-page":"1014","article-title":"Radiological properties of Next Generation Theranostics (Cu-64\/Cu-67)","volume":"58","author":"Biggin","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.drudis.2018.04.002","article-title":"The emerging role of copper-64 radiopharmaceuticals as cancer theranostics","volume":"23","author":"Boschi","year":"2018","journal-title":"Drug Discov. Today"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22","DOI":"10.2174\/1874471011666171211161851","article-title":"Radiopharmaceuticals Labelled with Copper Radionuclides: Clinical Results in Human Beings","volume":"11","author":"Follacchio","year":"2018","journal-title":"Curr. RadioPharm."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chhabra, A., and Thakur, M.L. (2022). Theragnostic radionuclide pairs for prostate cancer Management: 64Cu\/67Cu, can be a budding hot duo. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112787"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.peptides.2008.12.003","article-title":"Structure-activity relationships of novel peptide agonists of the human bradykinin B2 receptor","volume":"30","author":"Bovenzi","year":"2009","journal-title":"Peptides"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1021\/bi981727r","article-title":"Overexpression and functional characterization of kinin receptors reveal subtype-specific phosphorylation","volume":"38","author":"Blaukat","year":"1999","journal-title":"Biochemistry"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"C\u00f4t\u00e9, J., Bovenzi, V., Savard, M., Dubuc, C., Fortier, A., Neugebauer, W., Tremblay, L., Muller-Esterl, W., Tsanaclis, A.M., and Lepage, M. (2012). Induction of selective blood-tumor barrier permeability and macromolecular transport by a biostable kinin B1 receptor agonist in a glioma rat model. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037485"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ccr.2010.05.026","article-title":"Integrative genomic profiling of human prostate cancer","volume":"18","author":"Taylor","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1471-2407-12-96","article-title":"Characterization of colon cancer cells: A functional approach characterizing CD133 as a potential stem cell marker","volume":"12","author":"Schneider","year":"2012","journal-title":"BMC Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0969-8051(96)00157-6","article-title":"Efficient production of high specific activity 64Cu using a biomedical cyclotron","volume":"24","author":"McCarthy","year":"1997","journal-title":"Nucl. Med. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Sikpa, D., Whittingstall, L., Savard, M., Lebel, R., C\u00f4t\u00e9, J., McManus, S., Chemtob, S., Fortin, D., Lepage, M., and Gobeil, F. (2020). Pharmacological Modulation of Blood\u2013Brain Barrier Permeability by Kinin Analogs in Normal and Pathologic Conditions. Pharmaceuticals, 13.","DOI":"10.3390\/ph13100279"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Gagnon, M., Savard, M., Tran, T.M.H., Vincent, L., Moquin, A., Tremblay, P., Roucou, X., Dory, Y., and Gobeil, F. (2023). Evaluation of Novel B1R\/B2R Agonists Containing TRIOZAN\u2122 Nanoparticles for Targeted Brain Delivery of Antibodies in a Mouse Model of Alzheimer Disease. Molecules, 28.","DOI":"10.3390\/molecules28135206"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.neo.2014.07.010","article-title":"PACE4-based molecular targeting of prostate cancer using an engineered 64Cu-radiolabeled peptide inhibitor","volume":"16","author":"Couture","year":"2014","journal-title":"Neoplasia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1021\/bc3002437","article-title":"Novel radiolabeled peptides for breast and prostate tumor PET imaging: 64Cu\/and 68Ga\/NOTA-PEG-[D-Tyr(6),betaAla(11),Thi(13),Nle(14)]BBN(6-14)","volume":"23","author":"Fournier","year":"2012","journal-title":"Bioconjug Chem"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1476-5381.1996.tb15401.x","article-title":"Receptors for kinins in the human isolated umbilical vein","volume":"118","author":"Gobeil","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(98)00165-4","article-title":"Bradykinin receptors and their antagonists","volume":"348","author":"Regoli","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.peptides.2008.12.018","article-title":"Novel kinin B1 receptor agonists with improved pharmacological profiles","volume":"30","author":"Savard","year":"2009","journal-title":"Peptides"},{"key":"ref_44","first-page":"6864","article-title":"Subcellular Localization of Radiolabeled Somatostatin Analogues: Implications for Targeted Radiotherapy of Cancer","volume":"63","author":"Wang","year":"2003","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1002\/jcp.27103","article-title":"Antitumor activity of cell-penetrant kinin B1 receptor antagonists in human triple-negative breast cancer cells","volume":"234","author":"Dubuc","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bergeron, M., Cadorette, J., Tetrault, M.-A., Beaudoin, J.-F., Leroux, J.-D., Fontaine, R., and Lecomte, R. (2014). Imaging performance of LabPET APD-based digital PET scanners for pre-clinical research. Phys. Med. Biol, 59.","DOI":"10.1088\/0031-9155\/59\/3\/661"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Khosravifarsani, M., Ait-Mohand, S., Paquette, B., Sanche, L., and Gu\u00e9rin, B. (2022). In vivo behavior of [64Cu] NOTA-terpyridine platinum, a novel chemo-radio-theranostic agent for imaging, and therapy of colorectal cancer. Front. Med., 9.","DOI":"10.3389\/fmed.2022.975213"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6814","DOI":"10.1073\/pnas.93.13.6814","article-title":"Radioimmunotherapy with a 64Cu-labeled monoclonal antibody: A comparison with 67Cu","volume":"93","author":"Connett","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"M\u00e9tivier, C., Le Sa\u00ebc, P., Gaschet, J., Chauvet, C., Marionneau-Lambot, S., Hofgaard, P.O., Bogen, B., Pineau, J., Le Bris, N., and Tripier, R. (2023). Preclinical evaluation of a 64Cu-based theranostic approach in a murine model of multiple myeloma. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071817"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Milot, M.C., Belissant-Benesty, O., Dumulon-Perreault, V., Ait-Mohand, S., Geha, S., Richard, P.O., Rousseau, E., and Guerin, B. (2023). Theranostic 64Cu-DOTHA2-PSMA allows low toxicity radioligand therapy in mice prostate cancer model. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1073491"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.nucmedbio.2010.08.009","article-title":"Internal radiotherapy with copper-64-diacetyl-bis (N4-methylthiosemicarbazone) reduces CD133+ highly tumorigenic cells and metastatic ability of mouse colon carcinoma","volume":"38","author":"Yoshii","year":"2011","journal-title":"Nuc. Med. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1093\/jnci\/djr393","article-title":"Assessment of Ki67 in breast cancer: Recommendations from the International Ki67 in Breast Cancer working group","volume":"103","author":"Dowsett","year":"2011","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_53","first-page":"1164","article-title":"Theranostic potential of a new [64Cu]-radiolabeled R-954 conjugate for kinin B1R positive tumors","volume":"57","author":"Savard","year":"2016","journal-title":"J. Nucl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.lfs.2012.10.008","article-title":"Tumor angiogenesis and lymphangiogenesis: Tumor\/endothelial crosstalk and cellular\/microenvironmental signaling mechanisms","volume":"92","author":"Gomes","year":"2013","journal-title":"Life Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6352","DOI":"10.1126\/science.aan2507","article-title":"A pathology atlas of the human cancer transcriptome","volume":"357","author":"Uhlen","year":"2017","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1021\/acs.bioconjchem.8b00225","article-title":"Radiometal-Dependent Biological Profile of the Radiolabeled Gastrin-Releasing Peptide Receptor Antagonist SB3 in Cancer Theranostics: Metabolic and Biodistribution Patterns Defined by Neprilysin","volume":"29","author":"Lymperis","year":"2018","journal-title":"Bioconjug. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lau, J., Rousseau, J., Kwon, D., B\u00e9nard, F., and Lin, K.-S. (2020). A systematic review of molecular imaging agents targeting bradykinin B1 and B2 receptors. Pharmaceuticals, 13.","DOI":"10.3390\/ph13080199"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Shukuri, M., Onoe, S., Karube, T., Mokudai, R., Wakui, H., Asano, H., Murai, S., and Akizawa, H. (2024). Assessment of Radiolabelled Derivatives of R954 for Detection of Bradykinin B1 Receptor in Cancer Cells: Studies on Glioblastoma Xenografts in Mice. Pharmaceuticals, 17.","DOI":"10.3390\/ph17070902"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1038\/s41467-023-36377-4","article-title":"Radiochemistry for positron emission tomography","volume":"14","author":"Rong","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1124\/pr.57.1.2","article-title":"International union of pharmacology. XLV. Classification of the kinin receptor family: From molecular mechanisms to pathophysiological consequences","volume":"57","author":"Marceau","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Moller, T.C., Moo, E.V., Inoue, A., Pedersen, M.F., and Brauner-Osborne, H. (2024). Characterization of the real-time internalization of nine GPCRs reveals distinct dependence on arrestins and G proteins. Biochim. Biophys. Acta Mol. Cell Res., 1871.","DOI":"10.1016\/j.bbamcr.2023.119584"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.cbpa.2021.06.008","article-title":"Reducing the renal retention of low- to moderate-molecular-weight radiopharmaceuticals","volume":"63","author":"Chigoho","year":"2021","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1053\/j.semnuclmed.2016.04.006","article-title":"Renal Function Assessment During Peptide Receptor Radionuclide Therapy","volume":"46","author":"Erbas","year":"2016","journal-title":"Semin. Nucl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.2967\/jnumed.110.075101","article-title":"Renal toxicity of radiolabeled peptides and antibody fragments: Mechanisms, impact on radionuclide therapy, and strategies for prevention","volume":"51","author":"Vegt","year":"2010","journal-title":"J. Nucl. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/j.peptides.2011.07.023","article-title":"The bradykinin B1 receptor antagonist R-954 inhibits Ehrlich tumor growth in rodents","volume":"32","author":"Fernandes","year":"2011","journal-title":"Peptides"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1515\/hsz-2015-0246","article-title":"Safety and pharmacokinetics of a kinin B1 receptor peptide agonist produced with different counter-ions","volume":"397","author":"Savard","year":"2016","journal-title":"Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"806","DOI":"10.4161\/cbt.25327","article-title":"Dual kinin B1 and B2 receptor activation provides enhanced blood-brain barrier permeability and anticancer drug delivery into brain tumors","volume":"14","author":"Savard","year":"2013","journal-title":"Cancer Biol. Ther."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/9\/1215\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:15Z","timestamp":1760035695000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/9\/1215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":67,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["pharmaceutics17091215"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17091215","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]}}}