{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:39:12Z","timestamp":1777865952804,"version":"3.51.4"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020417","name":"Consejo Mexiquense de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["FICDTEM-2021-008"],"award-info":[{"award-number":["FICDTEM-2021-008"]}],"id":[{"id":"10.13039\/501100020417","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Recently, we reported a new fibroblast activation protein (FAP) inhibitor radiopharmaceutical based on the 99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (99mTc-HYNIC-D-Alanine-BoroPro)(99mTc-HYNIC-iFAP) structure for tumor microenvironment SPECT imaging. This research aimed to synthesize 68Ga-[2,2\u2032,2\u2033,2\u2034-(2-(4-(2-(5-(((S)-1-((S)-2-boronopyrrolidin-1-yl)-1-oxopropan-2-yl)carbamoyl)pyridin-2-yl)hydrazine-1-carbothioamido)benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid] (68Ga-DOTA-D-Alanine-BoroPro)(68Ga-iFAP) as a novel radiotracer for PET imaging and evaluate its usefulness for FAP expression in malignant and non-malignant tissues. The coupling of p-SCN-benzene DOTA with HYNIC-iFAP was used for the chemical synthesis and further labeling with 68Ga. Radiochemical purity was verified by radio-HPLC. The specificity of 68Ga-iFAP was evaluated in HCT116 cells, in which FAP expression was verified by immunofluorescence and Western blot. Biodistribution and biokinetic studies were performed in murine models. 68Ga-iFAP uptake at the myocardial level was assessed in mice with induced infarction. First-in-human images of 68Ga-iFAP in healthy subjects and patients with myocardial infarction, glioblastoma, prostate cancer, and breast cancer were also obtained. DOTA-D-Alanine BoroPro was prepared with a chemical purity of 98% and was characterized by UPLC mass spectroscopy, FT-IR, and UV-vis. The 68Ga-iFAP was obtained with a radiochemical purity of &gt;95%. In vitro and in vivo studies demonstrated 68Ga-iFAP-specific recognition for FAP, rapid renal elimination, and adequate visualization of the glioblastoma, breast tumor, prostate cancer, and myocardial infarction sites. The results of this research justify further dosimetry and clinical trials to establish the specificity and sensitivity of 68Ga-iFAP PET for FAP expression imaging.<\/jats:p>","DOI":"10.3390\/pharmaceutics16040532","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T09:28:06Z","timestamp":1712914086000},"page":"532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["68Ga-DOTA-D-Alanine-BoroPro Radiotracer for Imaging of the Fibroblast Activation Protein in Malignant and Non-Malignant Diseases"],"prefix":"10.3390","volume":"16","author":[{"given":"Diana","family":"Trujillo-Ben\u00edtez","sequence":"first","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"},{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4082-3816","authenticated-orcid":false,"given":"Myrna","family":"Luna-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 G.","family":"Aguirre-De Paz","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"},{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-7324","authenticated-orcid":false,"given":"Pedro","family":"Cruz-Nova","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Bravo-Villegas","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9057-6109","authenticated-orcid":false,"given":"Joel E.","family":"Vargas-Ahumada","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Instituto Nacional de Cardiolog\u00eda, Mexico City 14000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-913X","authenticated-orcid":false,"given":"Paola","family":"Vallejo-Armenta","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Instituto Nacional de Cancerolog\u00eda, Mexico City 14000, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-6791","authenticated-orcid":false,"given":"Enrique","family":"Morales-Avila","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9480-4621","authenticated-orcid":false,"given":"Nallely","family":"Jim\u00e9nez-Mancilla","sequence":"additional","affiliation":[{"name":"C\u00e1tedras, CONACyT, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5441-0863","authenticated-orcid":false,"given":"Rigoberto","family":"Oros-Pantoja","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Toluca 50180, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5903-1598","authenticated-orcid":false,"given":"Clara","family":"Santos-Cuevas","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7520-461X","authenticated-orcid":false,"given":"Erika","family":"Azor\u00edn-Vega","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-8412","authenticated-orcid":false,"given":"Blanca","family":"Ocampo-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0296-7605","authenticated-orcid":false,"given":"Guillermina","family":"Ferro-Flores","sequence":"additional","affiliation":[{"name":"Department of Radioactive Materials, Instituto Nacional de Investigaciones Nucleares, Ocoyoacac 52750, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.2967\/jnumed.120.244806","article-title":"The latest developments in imaging of fibroblast activation protein","volume":"62","author":"Altmann","year":"2021","journal-title":"J. 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