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Macroscopic Fluorescence Lifetime Imaging for Monitoring of Drug–Target Engagement

Part of the Methods in Molecular Biology book series (MIMB,volume 2394)

Abstract

Precision medicine promises to improve therapeutic efficacy while reducing adverse effects, especially in oncology. However, despite great progresses in recent years, precision medicine for cancer treatment is not always part of routine care. Indeed, the ability to specifically tailor therapies to distinct patient profiles requires still significant improvements in targeted therapy development as well as decreases in drug treatment failures. In this regard, preclinical animal research is fundamental to advance our understanding of tumor biology, and diagnostic and therapeutic response. Most importantly, the ability to measure drug–target engagement accurately in live and intact animals is critical in guiding the development and optimization of targeted therapy. However, a major limitation of preclinical molecular imaging modalities is their lack of capability to directly and quantitatively discriminate between drug accumulation and drug–target engagement at the pathological site. Recently, we have developed Macroscopic Fluorescence Lifetime Imaging (MFLI) as a unique feature of optical imaging to quantitate in vivo drug–target engagement. MFLI quantitatively reports on nanoscale interactions via lifetime-sensing of Förster Resonance Energy Transfer (FRET) in live, intact animals. Hence, MFLI FRET acts as a direct reporter of receptor dimerization and target engagement via the measurement of the fraction of labeled-donor entity undergoing binding to its respective receptor. MFLI is expected to greatly impact preclinical imaging and also adjacent fields such as image-guided surgery and drug development.

Key words

  • Fluorescence lifetime imaging (FLI)
  • Forster resonance energy transfer (FRET)
  • Target engagement
  • Hyperspectral imaging
  • Structured Light Imaging
  • Receptor
  • Near infrared

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Acknowledgments

Authors thank current and previous members of the Barroso and Intes laboratories for their effort in the development and validation of these technologies. This work is funded by the National Institutes of Health grants R01CA250636, R01CA207725, and R01CA237267. The authors have declared that no competing interest exists.

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Correspondence to Margarida Barroso .

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Ochoa, M., Rudkouskaya, A., Smith, J.T., Intes, X., Barroso, M. (2022). Macroscopic Fluorescence Lifetime Imaging for Monitoring of Drug–Target Engagement. In: Rasooly, A., Baker, H., Ossandon, M.R. (eds) Biomedical Engineering Technologies. Methods in Molecular Biology, vol 2394. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1811-0_44

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  • DOI: https://doi.org/10.1007/978-1-0716-1811-0_44

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