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However, their clinical application is still impeded by rapid systemic clearance and limited retention within tumor tissues. Therefore, the development of advanced radiopharmaceuticals with good tumor specificity and prolonged intratumoral retention is highly critical for effective tumor imaging and therapy. Herein, we rationally design and synthesize a furin enzyme\u2010responsive radioactive molecule RVRR\u2010TPE that consists of a furin enzyme\u2010specific peptide substrate Arg\u2010Val\u2010Arg\u2010Arg (RVRR), a hydrophobic fluorophore tetraphenylethene (TPE) with aggregation\u2010induced emission (AIE) characteristics, and a phenol unit for Iodine isotope labeling. Probes RVRR\u2010TPE were self\u2010assembled into large nanoparticles in furin enzyme\u2010positive cancer cells, resulting in enhanced uptake and prolonged retention. In vivo studies demonstrated that the\n                    <jats:sup>125<\/jats:sup>\n                    I or\n                    <jats:sup>131<\/jats:sup>\n                    I\u2010labeled probes could be used for Single\u2010Photon Emission Computed Tomography (SPECT) tumor imaging and significantly suppressed the growth of furin\u2010positive HCT116 colon tumor with great therapeutic effect. This furin\u2010mediated aggregation strategy to prolong retention effect offers a promising platform for effective radionuclide imaging and treatment of various malignancies.\n                  <\/jats:p>","DOI":"10.1002\/smll.73679","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:36:08Z","timestamp":1778056568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Furin\u2010Mediated Intracellular Aggregation of Radioactive Molecules for Enhanced Radionuclide Imaging and Tumor Therapy"],"prefix":"10.1002","volume":"22","author":[{"given":"Mei","family":"Hu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Collaborative Innovation Centre of Radiological Medicine of Jiangsu Higher Education Institutions Soochow University  Suzhou 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