MRI contrast agents (CAs) feature coordinated water molecule(s) (aqua ligands), which renders them unsuitable for magnetic resonance (MR) temperature mapping because of their resulting sensitivity to metabolic and physiological changes and/or their tendency to release toxic Gd3+ cations. Herein, we introduce an approach to temperature mapping based upon a coordinatively saturated gadolinium (Gd)-based metal-organic framework (MOF) that exhibits enhanced proton relaxation and high temperature sensitivity. The stable, non-toxic Gd zeolite-like MOF Gd-ZMOF was observed to generate a large enhancement in contrast as a result of a large (70%) contribution from second-sphere water relaxivity. Temperature mapping by clinical CAs and Gd-ZMOF by means of longitudinal (T1) relaxivity was investigated. Gd-ZMOF enabled the visualization of small temperature changes, especially in the thermal therapy region (41°C–45°C). In vivo thermal imaging demonstrates the feasibility of Gd-ZMOF as an MR thermometer and as a potential theranostic. Whereas non-invasive magnetic resonance (MR) thermometry offers high spatial and temporal resolution for precise monitoring of temperature rises induced during cancer treatment, it suffers from low temperature sensitivity and image contrast. The widespread use of soluble paramagnetic Gd(III) contrast agents (CAs) in MR imaging addresses contrast issues, but their use in MR thermometry is mitigated by poor temperature sensitivity. Here, we introduce the prototype of a new class of CAs based on an insoluble Gd(III) metal-organic framework, Gd-ZMOF, that exhibits much higher thermal sensitivity than the current generation of CAs. Nanoparticles of Gd-ZMOF are bioavailable and biocompatible and exhibit benchmark performance with respect to in vitro and in vivo MR thermal mapping. This discovery could represent a new paradigm for CAs since Gd-ZMOF is highly porous and could therefore serve as a theranostic agent. Gd-ZMOF nanoparticles exhibit benchmark performance with respect to in vitro and in vivo MRI thermal mapping and afford fundamental insight into the design of a new generation of insoluble contrast agents with high stability, low toxicity, and benchmark thermal sensitivity.
A Gadolinium(III) Zeolite-like Metal-Organic-Framework-Based Magnetic Resonance Thermometer
Gianolio E.;Aime S.;
2019-01-01
Abstract
MRI contrast agents (CAs) feature coordinated water molecule(s) (aqua ligands), which renders them unsuitable for magnetic resonance (MR) temperature mapping because of their resulting sensitivity to metabolic and physiological changes and/or their tendency to release toxic Gd3+ cations. Herein, we introduce an approach to temperature mapping based upon a coordinatively saturated gadolinium (Gd)-based metal-organic framework (MOF) that exhibits enhanced proton relaxation and high temperature sensitivity. The stable, non-toxic Gd zeolite-like MOF Gd-ZMOF was observed to generate a large enhancement in contrast as a result of a large (70%) contribution from second-sphere water relaxivity. Temperature mapping by clinical CAs and Gd-ZMOF by means of longitudinal (T1) relaxivity was investigated. Gd-ZMOF enabled the visualization of small temperature changes, especially in the thermal therapy region (41°C–45°C). In vivo thermal imaging demonstrates the feasibility of Gd-ZMOF as an MR thermometer and as a potential theranostic. Whereas non-invasive magnetic resonance (MR) thermometry offers high spatial and temporal resolution for precise monitoring of temperature rises induced during cancer treatment, it suffers from low temperature sensitivity and image contrast. The widespread use of soluble paramagnetic Gd(III) contrast agents (CAs) in MR imaging addresses contrast issues, but their use in MR thermometry is mitigated by poor temperature sensitivity. Here, we introduce the prototype of a new class of CAs based on an insoluble Gd(III) metal-organic framework, Gd-ZMOF, that exhibits much higher thermal sensitivity than the current generation of CAs. Nanoparticles of Gd-ZMOF are bioavailable and biocompatible and exhibit benchmark performance with respect to in vitro and in vivo MR thermal mapping. This discovery could represent a new paradigm for CAs since Gd-ZMOF is highly porous and could therefore serve as a theranostic agent. Gd-ZMOF nanoparticles exhibit benchmark performance with respect to in vitro and in vivo MRI thermal mapping and afford fundamental insight into the design of a new generation of insoluble contrast agents with high stability, low toxicity, and benchmark thermal sensitivity.
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