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

  • 0State Key Laboratory of Magnetic Resonance Spectroscopy and Imaging, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences-Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430071, P. R. China.
Analytical Chemistry +

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April 22, 2025

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April 22, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study introduces a novel dual-enhanced magnetic resonance imaging (MRI) probe, CFDEVDFFFK(Fmoc)-Gd, which detects caspase-3 activity in apoptotic tumor cells. The probe enables simultaneous 1H and 19F MRI, improving visualization of treatment response.

Area Of Science

  • Biomedical Imaging
  • Molecular Imaging
  • Cancer Research

Background

  • Caspase-3 (Cas-3) is vital for apoptosis, a key process in tumor response to chemotherapy.
  • Developing molecular imaging probes for apoptotic signals is crucial for improving cancer treatment outcomes.
  • Achieving dual-enhanced bimodal probes in a single molecule presents a significant challenge.

Purpose Of The Study

  • To develop a 1H/19F dual-enhanced MRI probe responsive to caspase-3 for in vivo imaging of apoptotic cells.
  • To enable simultaneous detection of apoptotic signals using both 1H and 19F MRI modalities.
  • To assess the probe's efficacy in visualizing caspase-3 activity in tumors during chemotherapy.

Main Methods

  • Development of a novel probe, CFDEVDFFFK(Fmoc)-Gd, designed to be cleaved by caspase-3.
  • Investigation of the probe's self-assembly into nanofibers upon caspase-3 activation, leading to signal enhancement.
  • Evaluation of the probe's performance in vitro and in vivo using 1H and 19F MRI in a 4T1 tumor model.

Main Results

  • The probe CFDEVDFFFK(Fmoc)-Gd effectively detects caspase-3 activity, leading to dual-enhanced 1H and 19F MRI signals.
  • Caspase-3 activation resulted in a significant increase in longitudinal relaxivity (r1) from 9.38 to 23.24 mM-1 s-1 at 0.5 T.
  • In vivo imaging demonstrated enhanced 1H MRI signals in apoptotic 4T1 tumors, three times greater than Gd-DTPA, and a notable recovery of 19F MRI signal.

Conclusions

  • CFDEVDFFFK(Fmoc)-Gd serves as an effective dual-enhanced MRI probe for reporting tumor apoptosis.
  • The probe facilitates in vivo visualization of caspase-3 activity, offering a promising tool for assessing antitumor efficacy.
  • This dual-modal imaging approach enhances the detection of apoptotic cells, aiding in preliminary evaluation of therapeutic responses.