The paper "Quantitative imaging of receptor-ligand engagement in intact live animals" was chosen as the cover story for Issue 286 of the Journal of Controlled Release. The paper is a collaboration between Rensselaer and Albany Medical College and is authored by Alena Rudkouskaya, Nattawut Sinsuebphon, Jamie Ward, Kate Tubbesing, Xavier Intes, and Margarida Barroso.
The abstract of the paper is shown below:
Maintaining an intact tumor environment is critical for quantitation of receptor-ligand engagement in a targeted drug development pipeline. However, measuring receptor-ligand engagement in vivo and non-invasively in preclinical settings is extremely challenging. We found that quantitation of intracellular receptor-ligand binding can be achieved using whole-body macroscopic lifetime-based Förster Resonance Energy Transfer (FRET) imaging in intact, live animals bearing tumor xenografts. We determined that FRET levels report on ligand binding to transferrin receptors conversely to raw fluorescence intensity. FRET levels in heterogeneous tumors correlate with intracellular ligand binding but strikingly, not with ubiquitously used ex vivo receptor expression assessment. Hence, MFLI-FRET provides a direct measurement of systemic delivery, target availability and intracellular drug delivery in preclinical studies. Here, we have used MFLI to measure FRET longitudinally in intact and live animals. MFLI-FRET is well-suited for guiding the development of targeted drug therapy in heterogeneous tumors in intact, live small animals.
The paper can be found at:
https://doi.org/10.1016/j.jconrel.2018.07.032