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Adv."],"published-print":{"date-parts":[[2026,9,18]]},"abstract":"<jats:p>Pancreatic cancer (PC) is a highly aggressive and lethal malignancy with extremely poor patient survival rates. The lack of biomarkers and deep tissue detection barriers has presented long-standing and unsolved issues, severely hindering the early diagnosis of PC even in living rodent models. Here, we report a renal-clearable leucine aminopeptidase (LAP)\u2013activatable fluorescence probe, overturning the probe\u2019s pharmacokinetics from the liver to kidney pathway (90% of the injection dosage). This strategy reduces interference in the liver and enables LAP as a biomarker for PC detection in murine models. After in situ response with LAP in the pancreas, renal-clearable fluorogenic fragments could be efficiently excreted into the urine, thus addressing the depth barriers of PC. 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