Work

Caspase-3-Responsive Dual-Enhanced 1H/19F MRI Bimodal Probe for In Vivo Tumor Apoptosis Imaging

Year: 2025

Type: article

Abstract: Caspase-3 (Cas-3) is a crucial cysteine protease involved in executing cell apoptosis, a process that is a hallmark of tumor cell apoptosis response to chemotherapy. Developing molecular imaging probes that specifically detect apoptotic signals during tumor treatment is considered to be one of the most important and effective strategies for reducing cancer-associated death rates and improving treatment outcomes. However, achieving a dual-enhanced bimodal probe in a single molecule remains a significant challenge. In this study, we developed a 1 H/ 19 F dual-enhanced magnetic resonance imaging (MRI) probe, CF 3 DEVDFFFK(Fmoc)-Gd, responsive to caspase-3 for in vivo imaging of apoptotic cells. Upon interaction with caspase-3, CF 3 DEVDFFFK(Fmoc)-Gd efficiently splits into two components CF 3 DEVD and FFFK(Fmoc)-C 2 -Gd, where FFFK(Fmoc)-C 2 -Gd subsequently self-assembles into nanofibers. This process activates both 19 F MRI and 1 H MRI, with longitudinal relaxivity ( r 1 ) increasing from 9.38 ± 0.22 to 23.24 ± 2.33 mM –1 s –1 at 0.5 T and turning on the 19 F MRI signal due to the absence of the paramagnetic relaxation enhancement (PRE) effect. In vivo imaging results demonstrated that, after systemic administration, CF 3 DEVDFFFK(Fmoc)-Gd effectively accumulated in apoptotic 4T1 tumor tissues, resulting in significantly enhanced 1 H MRI signals for visualization of caspase-3 activity in doxorubicin-treated apoptotic 4T1 tumor tissues, with signal intensity three times greater than that of Gd-DTPA. 19 F MRI further complemented 1 H MRI, with a notable recovery of the 19 F MRI signal after intratumoral injection. These results confirm that CF 3 DEVDFFFK(Fmoc)-Gd effectively reports tumor apoptosis through combined 1 H and 19 F MRI, offering a promising approach for the preliminary assessment of antitumor efficacy in vivo .

Source: Analytical Chemistry

DOI: 10.1021/acs.analchem.4c06853