Related Experiment Videos
Antigen-responsive molecular sensor enables real-time tumor-specific imaging
Hyunjin Kim1, Hak Soo Choi2, Seok-Ki Kim1
1Molecular Imaging and Therapy Branch, National Cancer Center, 323 Ilsan-ro, Goyang, Gyeonggi 10408, Republic of Korea.
Abstract:
Antibody-fluorophore conjugates have high potential for the specific fluorescence detection of target cancer cells in vitro and in vivo. However, the antibody-fluorophore conjugates described to date are inappropriate for real-time imaging of target cells because removal of unbound antibody is required to reduce background fluorescence before quantifiable analysis by microscopy. In addition, clinical applications of the conjugates have been limited by persistent background retention due to their long systemic circulation and nonspecific uptake. Here we report fast and real-time near-infrared fluorescence imaging of target cancer cells using an antigen-responsive molecular "on-off" sensor: the fluorescence of trastuzumab-ATTO680 conjugate is dark (i.e., turned off) in the extracellular region, while it becomes highly fluorescent (i.e., turned on) upon binding to the target antigen HER2 on cancer cell surface. This molecular switch enables fast and real-time imaging of target cancer cells in vitro and in vivo.
Insights
This study introduces a novel "on-off" molecular sensor for fast, real-time fluorescence imaging of cancer cells. The trastuzumab-ATTO680 conjugate becomes fluorescent only when bound to HER2, enabling clear detection without background noise.
Area of Science:
- Biomedical imaging
- Molecular diagnostics
- Cancer research
Background:
- Antibody-fluorophore conjugates offer potential for cancer cell detection but suffer from high background fluorescence.
- Current methods require removal of unbound antibodies, hindering real-time imaging and clinical application.
- Nonspecific uptake and long circulation times limit the clinical utility of existing conjugates.
Purpose of the Study:
- To develop a novel molecular sensor for fast and real-time fluorescence imaging of target cancer cells.
- To overcome limitations of high background noise and persistent retention associated with conventional antibody-fluorophore conjugates.
- To enable efficient in vitro and in vivo imaging of HER2-expressing cancer cells.
Main Methods:
- Development of an antigen-responsive molecular "on-off" sensor using trastuzumab-ATTO680 conjugate.
- Utilizing the fluorescence "on-off" property triggered by binding to the target antigen HER2.
- Application of the sensor for near-infrared fluorescence imaging of cancer cells.
Main Results:
- The trastuzumab-ATTO680 conjugate exhibits quenched fluorescence in the extracellular environment (off state).
- Upon binding to the HER2 antigen on cancer cells, the conjugate's fluorescence is significantly enhanced (on state).
- This molecular switch facilitates rapid and real-time imaging of target cancer cells in vitro and in vivo.
Conclusions:
- The antigen-responsive molecular "on-off" sensor enables unprecedented speed and clarity in cancer cell imaging.
- This innovative approach significantly reduces background noise, improving the accuracy of fluorescence detection.
- The developed sensor holds promise for enhanced real-time diagnostics and monitoring of HER2-positive cancers.