PET/NIR‐II fluorescence imaging and image‐guided surgery of breast cancer using a CD47‐specific nanobody

Abstract Accurate tumor localization and complete resection remain major challenges in breast cancer surgery. Here, we developed a CD47‐targeted dual‐modal imaging probe integrating positron emission tomography (PET) and second near‐infrared window (NIR‐II) fluorescence imaging to enhance preoperative diagnosis and intraoperative guidance. CD47 expression in human breast cancer tissues was confirmed by immunohistochemistry. Two nanobodies—C2 (anti‐CD47) and ABDC2 (C2 fused with an albumin‐binding domain for prolonged circulation)—were engineered and conjugated to IRDye800CW for NIR‐II imaging or radiolabeled with [ 18 F]AlF‒RESCA for PET. In both subcutaneous and orthotopic 4T1‐Luc breast cancer models, including metastatic lymph node models, [ 18 F]AlF‒RESCA‒C2/ABDC2 showed strong tumor accumulation, while NIR‐II fluorescence imaging enabled precise intraoperative identification and resection of primary and metastatic lesions. This dual‐modal platform offers a comprehensive solution for accurate tumor localization and real‐time surgical navigation, with promising implications for improving surgical outcomes in breast cancer.