In Vivo Quantitative Assessment of a Radiation Dose Based on Ratiometric Photoacoustic Imaging of Tumor Apoptosis

Accurately assessing the radiation level of tumors and surrounding tissues is of great significance for the optimization of clinical therapeutic interventions as well as minimizing the radiation-induced side effects. Therefore, the development of noninvasive and sensitive biological dosimeters is vital to achieve quantitative detection of a radiation dose in a living system. Herein, as a proof of concept, we report a tumor-targeted and caspase-3-activatable NIR fluorogenic probe AcDEVD-Cy-RGD consisting of a hemicyanine fluorophore as a signal reporter, a caspase-3 specific Asp-Glu-Val-Asp (DEVD) peptide, and a cyclic Arg-Gly-Asp peptide (cRGD) for tumor targeting. Upon cleavage with activated caspase-3, this probe not only displays the lighted-up NIR fluorescence, but also ratiometric photoacoustic (PA₇₁₀/PA₆₈₀) signals concurrently in a caspase-3 concentration-dependent manner, allowing for sensitive and quantitative detection of caspase-3 activity through both fluorescence and PA imaging, which provides the possibility for real-time monitoring of tumor cell apoptosis in a living system. More notably, we utilized this probe to successfully realize the direct visualization of tumor response to chemo- or radiotherapy and, for the first time, achieve the accurate estimation of radiation doses imparted to the tumors. We thus believe that our current strategy would offer an attractive and valuable means for the precise assessment of locally delivered radiation doses in various clinical settings.