Photochemical activation of endosomal escape of MRI-Gd-agents in tumor cells
Eliana Gianolio
Dipartimento di Chimica IFM e Centro di Imaging Molecolare, Università di Torino, Torino, Italy
Search for more papers by this authorFrancesca Arena
Dipartimento di Chimica IFM e Centro di Imaging Molecolare, Università di Torino, Torino, Italy
Search for more papers by this authorGustav J. Strijkers
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
Search for more papers by this authorKlaas Nicolay
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
Search for more papers by this authorCorresponding Author
Silvio Aime
Dipartimento di Chimica IFM e Centro di Imaging Molecolare, Università di Torino, Torino, Italy
Dipartimento di Chimica IFM e Centro di Imaging Molecolare, Università di Torino, Via Nizza 52, Torino, Italy===Search for more papers by this authorEliana Gianolio
Dipartimento di Chimica IFM e Centro di Imaging Molecolare, Università di Torino, Torino, Italy
Search for more papers by this authorFrancesca Arena
Dipartimento di Chimica IFM e Centro di Imaging Molecolare, Università di Torino, Torino, Italy
Search for more papers by this authorGustav J. Strijkers
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
Search for more papers by this authorKlaas Nicolay
Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
Search for more papers by this authorCorresponding Author
Silvio Aime
Dipartimento di Chimica IFM e Centro di Imaging Molecolare, Università di Torino, Torino, Italy
Dipartimento di Chimica IFM e Centro di Imaging Molecolare, Università di Torino, Via Nizza 52, Torino, Italy===Search for more papers by this authorAbstract
Endocytosis is a common internalization pathway for cellular labeling with MRI contrast agents. However, the entrapment of the Gd(III) complexes into endosomes results in a “quenching” of the attainable relaxivity when the number of Gd(III) complexes reaches the number of ca. 1 × 109/cell. Herein we show that the use of the newly developed photochemical internalization technique provides an efficient method for attaining the endosomal escape of GdHPDO3A molecules entrapped by pinocytosis into different kind of cells. Furthermore, it has been found that a new “quenching” limit is observed when the number of Gd-HPDO3A complexes is ca. five times higher than the value observed for the endosome entrapped conditions. The observed behavior is explained in terms of the attainment of the conditions in which the difference in proton relaxation rates between the cytoplasmic and the extracellular compartment is higher than the exchange rate of water molecules across the cellular membrane. The experimental data points have been reproduced by using a properly designed theoretical compartment T1-relaxation model. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.
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