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Photochemical activation of endosomal escape of MRI‐Gd‐agents in tumor cells
Author(s) -
Gianolio Eliana,
Arena Francesca,
Strijkers Gustav J.,
Nicolay Klaas,
Högset Anders,
Aime Silvio
Publication year - 2011
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.22586
Subject(s) - endosome , internalization , pinocytosis , endocytosis , compartment (ship) , biophysics , chemistry , quenching (fluorescence) , relaxation (psychology) , cytoplasm , extracellular , molecule , intracellular , cell , fluorescence , biochemistry , biology , physics , oceanography , organic chemistry , quantum mechanics , neuroscience , geology
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 × 10 9 /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 T 1 ‐relaxation model. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.