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A macromolecular reporter whose near‐infrared fluorescence is activated by a bladder cancer biomarker and that efficiently undergoes renal clearance was synthesized. It was used for real‐time in vivo imaging and ex vivo urinalysis of bladder cancer in living mice. Abstract. Bladder cancer (BC) is a prevalent disease with high morbidity and mortality; however, in vivo optical imaging of BC remains challenging because of the lack of cancer‐specific optical agents with high renal clearance. Herein, a macromolecular reporter (CyP1) was synthesized for real‐time near‐infrared fluorescence (NIRF) imaging and urinalysis of BC in living mice. Because of the high renal clearance (ca. 94 % of the injection dosage at 24 h post‐injection) and its cancer.

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