title: On the fate of MRI Gd-based contrast agents in cells. Evidence for extensive degradation of linear complexes upon endosomal internalization.
abstract: Commercial Gd-containing complexes are often used as MRI reporters in cellular labeling procedures as they are internalized into endosomes by pinocytosis. A methodology has been applied to assess the relative stability of three commercial Gd contrast agents following cellular uptake in fibroblasts and macrophages. It has been found that the acyclic series of Gd MRI contrast agents are degraded much more rapidly than their macrocyclic analogues, following endosomal internalization into living cells. This helps to explain their causal role in the development of nephrogenic systemic fibrosis in renally impaired patients. The methodology has also been applied to assess the fate of Gd-DTPA-BMA-loaded liposomes upon their endosomal internalization. Resistant liposomes prevent the degradation of the complex, whereas liposomes designed to release their payload in the acidic environments show a loss of integrity of Gd-DTPA-BMA analogous to the one observed upon internalization of the free complex.
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences, University of Torino, Via Nizza 52, Torino, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Di Gregorio
authors.forename: Eliana
authors.initials: E
authors.lastname: Gianolio
authors.forename: Rachele
authors.initials: R
authors.lastname: Stefania
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barutello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Digilio
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000737:chemistry* / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D041681:NIH 3T3 Cells; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D003287:Contrast Media; D005682:Gadolinium