{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:13:53Z","timestamp":1783660433713,"version":"3.55.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Fibroblast activation protein (FAP) is expressed by activated fibroblasts and selected vascular-associated stromal cells in tumors and non-malignant repair processes. Radiolabeled FAP inhibitors (FAPIs) allow PET mapping of FAP-accessible activated stroma, complementing tumor-cell metabolic imaging with FDG. This narrative review summarizes the biological basis of FAP targeting, radiopharmaceutical design, clinical imaging applications, benign fibro-inflammatory pitfalls, and early therapeutic development. FAPI PET can provide high lesion-to-background contrast in desmoplastic and low-FDG-avid tumors and in regions where physiologic FDG uptake complicates interpretation. The strongest current clinical scenarios include problem-solving in gastrointestinal cancers, peritoneal disease, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and biliary tract cancers, as well as whole-body assessment of target expression before therapy trials. However, FAPI uptake is not tumor specific; wound healing, post-treatment remodeling, fibrosis, arthritis, pancreatitis, liver disease, atherosclerosis, and other fibro-inflammatory or repair states require careful correlation with CT, MRI, FDG PET, clinical history, and follow-up. For therapy, high early PET contrast alone is insufficient. First-generation monomeric tracers may wash out rapidly, FAP expression is heterogeneous, and absorbed dose depends on ligand residence time, lesion architecture, perfusion, radionuclide range, normal-organ uptake, marrow reserve, and the fraction of disease that is FAP avid. Longer-retention ligands, dimeric or multimeric constructs, albumin-binding approaches, and beta- or alpha-emitter strategies are expanding clinical development, but prospective dosimetry and outcome data remain limited. Overall, current evidence supports FAPI PET as a complementary imaging method and selection tool for protocolized FAP-targeted radionuclide therapy rather than as a universal replacement for established imaging or a routine therapy platform. Future translation should emphasize standardized acquisition and reporting, disease-specific indications, benign uptake checkpoints, lesion-level dosimetry, physiologically relevant preclinical models, and prospective trials measuring management impact, toxicity, quality of life, and patient-relevant outcomes.<\/jats:p>","DOI":"10.3389\/fonc.2026.1895276","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:25:41Z","timestamp":1783657541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibroblast activation protein inhibitor radiotheranostics for imaging activated tumor stroma and guiding radionuclide therapy"],"prefix":"10.3389","volume":"16","author":[{"given":"Hangyu","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Radiology, Ningbo Hangzhou Bay Hospital (Ningbo Branch of Renji Hospital, Shanghai Jiao Tong University School of 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