MFLI-FRET as an analytical tool to monitor drug distribution and penetration in tumor xenografts, liver and bladder in intact, live animals (Conference Presentation)

Margarida Barroso; Alena Rudkouskaya; Nattawut Sinsuebphon; Xavier Intes

doi:10.1117/12.2507523

4 March 2019 MFLI-FRET as an analytical tool to monitor drug distribution and penetration in tumor xenografts, liver and bladder in intact, live animals (Conference Presentation)

Margarida Barroso, Alena Rudkouskaya, Nattawut Sinsuebphon, Xavier Intes

Author Affiliations +

Proceedings Volume 10859, Visualizing and Quantifying Drug Distribution in Tissue III; 108590D (2019) https://doi.org/10.1117/12.2507523
Event: SPIE BiOS, 2019, San Francisco, California, United States

Abstract

There is a great unmet need to non-invasively quantify the active versus passive delivery of drugs in preclinical studies. Quantifying probe-receptor interactions, or target engagement in living systems, is critical as it directly correlates with drug efficacy. We selected the transferrin receptor (TfR) as a target, since TfR is overexpressed in breast cancer cells. MFLI-FRET enables the quantification of transferrin (Tf) internalization into the cells by measuring FRET between receptor-bound Tf donor and acceptor near infrared (NIR) fluorophore pairs, based on the reduction of donor fluorophore lifetime in live intact mice. In this study we compared FRET levels in aggressively growing triple negative MDA-MB-231 breast cancer tumors to estrogen receptor positive T47D tumors, which are less dense and slowly growing. Unlike in T47D xenografts, in MDA-MB-231 tumors FRET donor fraction (FD%) was very low or undetectable in first few hours post injection. Only by 24-48 h p.i. FD% reached comparable to T47D FD% levels. Immunohistochemical analysis of excised tumors showed that TfR density levels were similar in both types of tumors. This suggests that ligand penetration inside the MDA-MB-231 tumors is impaired due to microenvironment features, such as the perfusion defects, elevated stroma stiffness and interstitial fluid pressure. We plan to measure functional blood flow using contrast-enhanced Doppler Ultrasound imaging in tumors to further validate MFLI-FRET data. Overall, MFLI-FRET is well suited for guiding the development of targeted drug therapy in preclinical studies as analytical tool to monitor and quantify drug penetration in heterogeneous breast cancer xenografts.

Conference Presentation

Citation Download Citation

Margarida Barroso, Alena Rudkouskaya, Nattawut Sinsuebphon, and Xavier Intes "MFLI-FRET as an analytical tool to monitor drug distribution and penetration in tumor xenografts, liver and bladder in intact, live animals (Conference Presentation)", Proc. SPIE 10859, Visualizing and Quantifying Drug Distribution in Tissue III, 108590D (4 March 2019); https://doi.org/10.1117/12.2507523

ACCESS THE FULL ARTICLE

INSTITUTIONAL
Select your institution to access the SPIE Digital Library.

SELECT YOUR INSTITUTION

PERSONAL
Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.

PERSONAL SIGN IN

No SPIE Account? Create one

PURCHASE THIS CONTENT

SUBSCRIBE TO DIGITAL LIBRARY

50 downloads per 1-year subscription

Members: $195

Non-members: $335 ADD TO CART

25 downloads per 1 - year subscription

Members: $145

Non-members: $250 ADD TO CART

PURCHASE SINGLE ARTICLE

Includes PDF, HTML & Video, when available

Members: $17.00

Non-members: $21.00 ADD TO CART

PROCEEDINGS
PRESENTATION

WATCH
PRESENTATION SAVE TO MY LIBRARY

GET CITATION

KEYWORDS

Tumors

Bladder

Liver

Breast cancer

Fluorescence resonance energy transfer

Near infrared

Receptors

Show All Keywords

Keywords/Phrases

Search In:

Publication Years