Dual-Modality SPECT and Viscosity-Responsive AIE Fluorescence Probe for Pancreatic Cancer Diagnosis and...

The accurate early diagnosis and achievement of R0 resection in pancreatic ductal adenocarcinoma (PDAC) remain formidable clinical challenges. Plectin-1, a protein that is overexpressed in PDAC, has been identified as a promising target for diagnostic applications. In this study, a novel dual-modality probe, designated PTP-QM-DOTA, was developed to specifically target plectin-1. The probe integrates the radionuclide ¹⁷⁷Lu with a viscosity-responsive aggregation-induced emission (AIE) fluorophore, QM, thereby enabling both preoperative single-photon emission computed tomography (SPECT) imaging and intraoperative fluorescence navigation. In comparison with a nontargeted control probe (HSP-QM-DOTA), PTP-QM-DOTA demonstrated a 23.95 ± 0.54-fold increase in fluorescence intensity in high-viscosity media (96% glycerol) relative to pure water, thus exhibiting pronounced viscosity-responsive behavior. The probe demonstrated high radiolabeling efficiency, excellent radiostability, and favorable biocompatibility, with no significant evidence of toxicity or organ damage observed. In vivo SPECT imaging clearly delineated PDAC tumors within 1 h postinjection, with tumor uptake reaching 6.44 ± 1.88% IA/g at 30 min postinjection. The AIE properties of the fluorophore substantially enhanced fluorescence intensity and the signal-to-noise ratio (SNR) in tumor regions, enabling precise tumor localization. The collective findings of the present study establish the first evidence for ¹⁷⁷Lu-PTP-QM-DOTA as a safe, reliable, and efficient dual-modality peptide probe with possible potential for integrated diagnosis and surgical guidance of PDAC.