University of Lisbon, Lisbon, Portugal
Targeted drug delivery systems call for non-invasive imaging technologies. The Barroso group at Albany Medical College, New York, is developing a unique, 3D whole body approach using Förster resonance energy transfer (FRET) tomography.
Transferrin (Tfn) plays an important role in carrying iron into cells via the Tfn receptor (TFR) binding. TFR is expressed in all cells and tissues, but is particularly prevalent in tumors. As such, it has been widely used in targeted drug delivery systems to deliver anti-cancer drugs specifically to tumors – an important and promising approach for the development of effective therapies in cancer applications. Recently, it has been shown that although both Tfn-targeted and non-targeted drug particles accumulate similarly within the tumor, only Tfn-targeted particles show strong anti-tumor activity due to increased internalization of the drug particles.
There is a need to develop a non-invasive imaging method to allow for the optimization of the delivery device. Currently, only biochemical-based approaches are available and require in vitro analysis of tumor tissues. Therefore a non-invasive imaging method would allow for the internal visualization of Tfn in an active environment.
In vivo imaging approach
Led by Professor Margarida Barroso, a group at the Center for Cardiovascular Sciences at the Albany Medical College (AMC), New York, is currently developing such an approach, aiming to use three-dimensional (3D) wholebody tomographic imaging to visualize receptor-mediated Tfn cellular uptake. The team plans to capitalize on the homodimeric nature of TFR and employ FRET to image in vivo the ability of tissues to take up near-infrared (NIR) iron-bound Tfn (Figure 1).
Dr. Barroso's research interests include the regulation of membrane trafficking pathways and of receptor-mediated cholesterol and iron transport in live cells. Dr. Barroso's imaging expertise includes small animal optical imaging, confocal, spectral imaging and TIRF microscopy, automated quantitative FRET and FLIM imaging, FRET biosensors, FRAP imaging, HCA/HTS, quantum dots and fluorophore development and quantitative tissue and cell imaging of cancer and epithelial biomarkers. Recently, Dr. Barroso's laboratory at AMC and Dr. Intes group at RPI have established a collaboration to employ whole-body in-vivo near-infrared FRET imaging to quantitate the receptor-mediated uptake of the near infrared-labeled transferin into tumor xenografts in live animals. The main goal of this exciting project is to develop a non-invasive whole-body imaging system to achieve the direct visualization of the delivery of transferrin-targeted particles into tumor cells.
- Venugopal, V., Chen, J., Barroso, M. and Intes, X. Quantitative tomographic imaging of intermolecular FRET in small animals. Biomedical Optical Express, 3: 3161-75; PMC3521293, 2012
- Talati, R., Vanderpoel, A., Eladdadi, A., Anderson, K., Abe, K. and Barroso, M. Automated Selection of Regions of Interest for Intensity-based FRET Analysis of Transferrin Endocytic Trafficking in Normal vs. Cancer Cells. Methods, Available online 28 August 2013, http://dx.doi.org/10.1016/j.ymeth.2013.08.017, 2013.
- Abe, K., Zhao, L., Periasamy, A., Intes, X. and Barroso, M. Non-Invasive In Vivo Imaging of Transferrin Internalization by Breast Cancer Cells and Tumors Using Near Infrared FRET FLIM. PlosOne, 11: e80269, PMC3836976, 2013.
- Wallrabe H, Elangovan M, Burchard A, Periasamy A and Barroso M. Confocal FRET microscopy to measure clustering of ligand-receptor complexes in endocytic membranes. Biophys J 85: 559-571, 2003.
- Wallrabe H, Stanley M, Periasamy A and Barroso M. One- and two-photon FRET microscopy to establish a clustered distribution of receptor-ligand complexes in endocytic membranes. J Biomed Opt 8: 339-346, 2003
- Elangovan M, Wallrabe H, Chen Y, Day RN, Barroso M and Periasamy A. Characterization of one- and two-photon excitation fluorescence resonance energy transfer microscopy. Methods 29: 58-73, 2003.
- Wallrabe H and Barroso M. FRET reveals the organization of different receptor-ligand complexes (polymeric IgA-R and Transferrin-R) in endocytic membranes of polarized MDCK cells. Proc. SPIE, Vol. 5323 (in press), Microscopy in the Biomedical Sciences IV; A. Periasamy (Ed.), 2004.