Photochemical activation of endosomal escape of MRI-Gd-agents in tumor cells

E. Gianolio, F. Arena, G.J. Strijkers, K. Nicolay, A. Högset, S. Aime

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)212-219
JournalMagnetic Resonance in Medicine
Volume65
Issue number1
DOIs
Publication statusPublished - 2011

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Endosomes
Pinocytosis
Endocytosis
Contrast Media
Protons
Neoplasms
Membranes
Water
gadoteridol

Cite this

Gianolio, E. ; Arena, F. ; Strijkers, G.J. ; Nicolay, K. ; Högset, A. ; Aime, S. / Photochemical activation of endosomal escape of MRI-Gd-agents in tumor cells. In: Magnetic Resonance in Medicine. 2011 ; Vol. 65, No. 1. pp. 212-219.
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Photochemical activation of endosomal escape of MRI-Gd-agents in tumor cells. / Gianolio, E.; Arena, F.; Strijkers, G.J.; Nicolay, K.; Högset, A.; Aime, S.

In: Magnetic Resonance in Medicine, Vol. 65, No. 1, 2011, p. 212-219.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Gianolio, E.

AU - Arena, F.

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AU - Högset, A.

AU - Aime, S.

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AB - 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.

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