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Here, LTZi\u2010MHI148 (Letrozole inhibitor bonding with MHI\u2010148 dye), a near\u2010infrared (NIR) fluorescent agent is developed, to target RhoJ (Ras Homolog Family Member J), a protein expressed in neonatal vasculature, for both imaging and therapy of early PDAC. This agent is synthesized by conjugating Letrozole with MHI\u2010148, exhibiting excellent NIR characteristics and photostability. In vitro studies showed that LTZi\u2010MHI148 selectively accumulated within pancreatic cancer cells through Organic Anion Transporting Polypeptide (OATP) transporters and bound to cytoplasmic RhoJ. In vivo, the probe effectively targeted neoangiogenesis and Pancreatic Intraepithelial Neoplasias (PanINs) in various PDAC models, including the orthotopic, ectopic, spontaneous, and tamoxifen\u2010induced tumors. Notably, LTZi\u2010MHI148 detected preneoplastic PanIN lesions with Overexpressed RhoJ and active neoangiogenesis in both spontaneous and tamoxifen\u2010induced PDAC murine models. Longitudinal imaging studies revealed that RhoJ\u2010targeted neoangiogenesis tracks lesion progression, highlighting LTZi\u2010MHI148's utility in monitoring disease progression. Furthermore, multiple LTZi\u2010MHI148 administrations attenuated PanINs to PDAC progression, suggesting its potential as a therapeutic intervention. These findings underscore the translational potential of LTZi\u2010MHI148 for the early detection and targeted therapy of PDAC, utilizing NIR\u2010I\/II imaging to monitor RhoJ overexpression in precancerous ductal neoplasia associated with neoangiogenesis.<\/jats:p>","DOI":"10.1002\/adhm.202402913","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T08:09:08Z","timestamp":1727424548000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Letrozole\u2010Based Near\u2010Infrared Dynamic Imaging Targeting Ductal\u2010Vascular RhoJ From Pancreatic Intraepithelial Neoplasia to Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8203-9715","authenticated-orcid":false,"given":"Zhi","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shenzhen People's Hospital (The Second Clinical Medical College Jinan University The First Affiliated Hospital Southern University of Science and Technology)  Shenzhen Guangdong 518020 China"},{"name":"School of Pharmaceutical Sciences Wuhan University  Wuhan Hubei 430071 China"},{"name":"Key Laboratory of Brain Cognition and Education Sciences Ministry of Education China Institute for Brain Research and Rehabilitation South China Normal University  Guangzhou Guangdong 510631 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7207-5568","authenticated-orcid":false,"given":"Zhuang","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Wuhan University  Wuhan Hubei 430071 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yishu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Brain Cognition and Education Sciences Ministry of Education China Institute for Brain Research and Rehabilitation South 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