{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:28:48Z","timestamp":1768782528490,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia, Portugal","doi-asserted-by":"publisher","award":["UID\/Multi\/04349\/2019"],"award-info":[{"award-number":["UID\/Multi\/04349\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia, Portugal","doi-asserted-by":"publisher","award":["PTDC\/MED-QUI\/1554\/2020"],"award-info":[{"award-number":["PTDC\/MED-QUI\/1554\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Several gastrin-releasing peptide receptor (GRPR) antagonists with improved in vivo behavior have been recently developed and tested in the clinic. However, despite the generally mild side effects of peptide receptor radionuclide therapy (PRRT), toxicity has been observed due to high doses delivered to nontarget tissues, especially in the kidneys and pancreas. Previous experiences with radiolabeled peptides opened a unique opportunity to explore GRPR pretargeting using clickable bombesin antagonists. Toward this goal, we used clickable DOTA-like radiocomplexes which have been previously evaluated by our group. We functionalized a potent GRPR antagonist with a clickable TCO moiety using two different linkers. These precursors were then studied to select the compound with the highest GRPR binding affinity and the best pharmacokinetics to finally explore the advantages of the devised pretargeting approach. Our results provided an important proof of concept toward the development of bioorthogonal approaches to GRPR-expressing cancers, which are worth investigating further to improve the in vivo results. Moreover, the use of clickable GRPR antagonists and DOTA\/DOTAGA derivatives allows for fine-tuning of their pharmacokinetics and metabolic stability, leading to a versatile synthesis of new libraries of (radio)conjugates useful for the development of theranostic tools toward GRPR-expressing tumors.<\/jats:p>","DOI":"10.3390\/pharmaceutics14122569","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T03:15:24Z","timestamp":1669173324000},"page":"2569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bioorthogonal Chemistry Approach for the Theranostics of GRPR-Expressing Cancers"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6740-8607","authenticated-orcid":false,"given":"Alice","family":"D\u2019Onofrio","sequence":"first","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"}]},{"given":"Francisco","family":"Silva","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7186-2060","authenticated-orcid":false,"given":"Lurdes","family":"Gano","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-1427","authenticated-orcid":false,"given":"Paula","family":"Raposinho","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2119-8293","authenticated-orcid":false,"given":"C\u00e9lia","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"}]},{"given":"Arkadiusz","family":"Sikora","sequence":"additional","affiliation":[{"name":"National Centre for Nuclear Research, Radioisotope Centre POLATOM, 05-400 Otwock, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0678-0891","authenticated-orcid":false,"given":"Monika","family":"Wycz\u00f3\u0142kowska","sequence":"additional","affiliation":[{"name":"National Centre for Nuclear Research, Radioisotope Centre POLATOM, 05-400 Otwock, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6882-751X","authenticated-orcid":false,"given":"Renata","family":"Miko\u0142ajczak","sequence":"additional","affiliation":[{"name":"National Centre for Nuclear Research, Radioisotope Centre POLATOM, 05-400 Otwock, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0650-1992","authenticated-orcid":false,"given":"Piotr","family":"Garnuszek","sequence":"additional","affiliation":[{"name":"National Centre for Nuclear Research, Radioisotope Centre POLATOM, 05-400 Otwock, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9164-0913","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Paulo","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"},{"name":"Departamento de Engenharia e Ci\u00eancias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Campus Tecnol\u00f3gico e Nuclear, Estrada Nacional 10, Km 139.7, 2695-066 Bobadela LRS, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/nyas.14100","article-title":"Peptide receptors as cancer drug targets","volume":"1455","author":"Moody","year":"2019","journal-title":"Ann. 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