Photochemical activation of endosomal escape of MRI-Gd-agents in tumor cells.
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.
Dipartimento di Chimica IFM e Centro di Imaging Molecolare, Università di Torino, Torino, Italy.
Eliana
E
Gianolio
Francesca
F
Arena
Gustav J
GJ
Strijkers
Klaas
K
Nicolay
Anders
A
Högset
Silvio
S
Aime
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics / Q000528:radiation effects; D011992:Endosomes / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods; D008027:Light; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D010777:Photochemistry / Q000379:methods; D051381:Rats; D013194:Staining and Labeling / Q000379:methods
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium