Fluorescence lifetime FRET non-invasive imaging of breast cancer xenografts provides a measure of target engagement in vivo (Conference Presentation)

Alena Rudkouskaya; Nattawut Sinsuebphon; Xavier Intes; Margarida Barroso

doi:10.1117/12.2257114

19 April 2017 Fluorescence lifetime FRET non-invasive imaging of breast cancer xenografts provides a measure of target engagement in vivo (Conference Presentation)

Alena Rudkouskaya, Nattawut Sinsuebphon, Xavier Intes, Margarida Barroso

Author Affiliations +

Proceedings Volume 10049, Molecular-Guided Surgery: Molecules, Devices, and Applications III; 1004908 (2017) https://doi.org/10.1117/12.2257114
Event: SPIE BiOS, 2017, San Francisco, California, United States

Abstract

Fluorescence Lifetime Förster Resonance Energy Transfer (FLIM-FRET) is a unique non-invasive imaging platform to monitor and quantify in vivo target engagement in pre-clinical studies. FLIM FRET is a valuable tool in targeted drug delivery due to its nanoscale-range molecular resolution that detects near-infrared labeled ligand binding to dimerized receptors followed by their uptake into cancer cells in vivo. Various imaging platforms, including PET, lack the ability to directly discriminate between unbound and internalized ligands. Since transferrin receptor (TfR) level is significantly elevated in cancer cells compared to non-cancerous cells, transferrin (Tf) has been successfully used in molecular imaging and targeted anti-cancer drug delivery. The dimeric nature of TfR allows for the quantification of Tf internalization into cancer cells by measuring FLIM FRET between receptor-bound Tf donor and acceptor NIR fluorophore pairs, based on the reduction of donor fluorophore lifetime in live mice. We analyzed tumor morphology, the level of expression of TfR, estrogen receptor (ER) and Tf accumulation in human breast cancer tumor xenografts. We found a remarkable heterogeneity of breast cancer tumors regarding their size, cell density, TfR and ER expression and Tf uptake. The results of this study confirm a strong correlation between in vivo NIR FLIM FRET and ex vivo evaluation of Tf uptake into tumor tissues, thus validating FD% as a robust measure of the target engagement of TfR-Tf in tumor cells in vivo.

Conference Presentation

Citation Download Citation

Alena Rudkouskaya, Nattawut Sinsuebphon, Xavier Intes, and Margarida Barroso "Fluorescence lifetime FRET non-invasive imaging of breast cancer xenografts provides a measure of target engagement in vivo (Conference Presentation)", Proc. SPIE 10049, Molecular-Guided Surgery: Molecules, Devices, and Applications III, 1004908 (19 April 2017); https://doi.org/10.1117/12.2257114

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KEYWORDS

In vivo imaging

Fluorescence resonance energy transfer

Tumors

Breast cancer

Cancer

Fluorescence lifetime imaging

Luminescence

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