Long-Term and Real-Time Post-External Radiotherapy Assessment Based on an In Situ Activatable Radiolabeled Platform

Long-term monitoring in postoperative assessment is essential for clinicians to assess the effectiveness of therapies and establish subsequent clinical pharmacotherapeutic plans. However, precise and real-time postoperative assessment is often overlooked, relying instead on various clinical histopathological and cytological assays or the experience of physicians. Therefore, it is urgent to develop a general strategy for long-term, real-time, and accurate postoperative assessment. Herein, we present a facile method utilizing radiolabeled probes for postradiotherapy assessment. The probe consists of a tumor-specific targeting group, an external radiotherapy-activated peptide sequence (DEVD), and a ¹⁷⁷Lu-1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA)-decorated tetraphenyl ethylene. This design not only avoids photobleaching and the limitations associated with traditional organic ligands for long-term monitoring but also achieves in situ aggregation at the lesion site, allowing for prolonged tumor retention over 96 h. This work serves as a glance at utilizing radiolabeled probes for postoperative assessment, broadening the possibilities for the design, application, and clinical translation of radionuclide-labeled probes.