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Positron Emission Tomography01:29

Positron Emission Tomography

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Positron emission tomography (PET) is a medical imaging technique involving radiopharmaceuticals — substances that emit short-lived radiation. Although the first PET scanner was introduced in 1961, it took 15 more years before radiopharmaceuticals were combined with the technique and revolutionized its potential.
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A PET-activated photosensitizer based on ROS-sensitive Trolox for tumor microenvironment-responsive imaging and

Hongyan An1, Du Liu1, Yuyan Li1

  • 1College of Chemistry & Chemical Engineering, Central South University, Changsha, Hunan 410083, China. benhuawang@csu.edu.cn.

Chemical Communications (Cambridge, England)
|September 12, 2025
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Summary

A novel photosensitizer, EtNBS-2C-Tro, is designed for reactive oxygen species (ROS)-responsive activation. This targeted approach enables effective tumor imaging and inhibition with minimal side effects.

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Area of Science:

  • Biomedical Engineering
  • Photodynamic Therapy
  • Chemical Biology

Background:

  • Photosensitizers are crucial for photodynamic therapy (PDT) but often lack specificity.
  • Reactive oxygen species (ROS) are implicated in various pathologies, including cancer.
  • Targeted activation of photosensitizers in the tumor microenvironment remains a challenge.

Purpose of the Study:

  • To develop a dormant photosensitizer, EtNBS-2C-Tro, that is activated by ROS.
  • To enable ROS-responsive fluorescence imaging in vivo.
  • To evaluate the therapeutic efficacy of EtNBS-2C-Tro for tumor inhibition.

Main Methods:

  • Design and synthesis of EtNBS-2C-Tro, a Trolox-modified benzo[a]phenoxazinium scaffold.
  • Investigation of photoinduced electron transfer (PET) for quenching and activation mechanisms.
  • In vitro and in vivo studies using tumor-bearing mice for ROS imaging and therapeutic evaluation.

Main Results:

  • EtNBS-2C-Tro exhibits quenched fluorescence and PDT activity in normal cells due to PET.
  • Elevated ROS in the tumor microenvironment oxidizes the chromanol ring, deactivating PET.
  • Restored fluorescence and photosensitizing activity enable targeted imaging and potent tumor inhibition with minimal side effects.

Conclusions:

  • EtNBS-2C-Tro serves as a ROS-activated probe for near-infrared fluorescence imaging of endogenous ROS.
  • The developed photosensitizer demonstrates significant tumor inhibition in vivo.
  • This ROS-responsive strategy offers a promising approach for targeted cancer therapy and diagnostics.