Polymer-Based Raman/PET Dual-Modal Probe for Preoperative Tumor Diagnosis and Intraoperative Image-Guided Surgery and Phototherapy

Integration of Raman imaging and positron emission tomography (PET) holds great promise for providing complementary information for precise cancer diagnosis and imaging-guided therapy. However, current existing Raman/PET dual-modal probes primarily rely on surface-enhanced Raman scattering, raising clinical concerns about the biosafety of the substrates. Herein, we developed a novel substrate-free Raman/PET probe-[ 18 F]-AS-DPPT-TT NPs, which integrates a biocompatible polymer DPPT-TT that possesses strong Raman signals and photothermal effects, along with radiolabeling by short-lived 18 F radionuclide and functionalization with tumor-targeting AS1411 aptamer. The [ 18 F]-AS-DPPT-TT NPs generate ultrasensitive resonance Raman signals under 785 nm excitation, due to their absorption peak closely matching the excitation light, and exhibit significant photothermal effects for tumor cell ablation under 808 nm excitation. In the orthotopic colon cancer mouse models, [ 18 F]-AS-DPPT-TT NPs enabled preoperative PET imaging for high-contrast whole-body tumor localization and simultaneously provided intraoperative Raman imaging for accurate tumor boundary delineation and micrometastasis detection (as small as 0.58 mm × 0.32 mm). Moreover, Raman imaging-guided surgery combined with photothermal therapy achieved complete elimination of primary and metastatic tumors, significantly decreasing the recurrence rates. This Raman/PET dual-modal probe effectively combines the strengths of Raman and PET imaging, providing a robust platform for comprehensive tumor management from preoperative planning to intraoperative intervention.