In vivo MRI visualization of different cell populations labeled with PARACEST agents (original) (raw)
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Inorganic Chemistry, 2018
The relaxivity of Gd(HP-DO3A) was studied as a function of pH and buffer composition in order to identify the main factors of the observed relaxation enhancement due to the exchange of the coordinated hydroxyl proton. It was established that the paramagnetic relaxation time, T 1M , of the coordinated hydroxyl proton is about 50% shorter than that of the protons in the coordinated water molecule. The control of the pK of the coordinated alcoholic −OH moiety in the ligand is fundamental to utilize the proton exchange enhanced relaxivity under physio/pathologic conditions. A new derivative of Gd(HP-DO3A) was synthesized by replacing the −CH 3 group with a −CF 3 moiety. In this complex, the −OH group becomes more acidic. Consequently, the maximum contribution of the proton exchange to the relaxivity is shifted to a lower pH region with the fluorinated ligand.
Amplification strategies in MR imaging: Activation and accumulation of sensing contrast agents (SCAs
Journal of Magnetic Resonance Imaging, 2006
We review new strategies for the development of Gd3+-based T1-relaxation agents and paramagnetic chemical exchange saturation transfer (PARACEST) “sensing” contrast agents (SCAs) designed specifically to detect small molecules or enzymatic activity in living systems. The first class of agents exhibits molecular “sensing” properties as a result of water coordination sphere effects, cleavage, or synthesis of reactive precursor compounds that recombine with macromolecules with the resultant formation of immobilized or rotationally constrained paramagnetic cations. This effect results in changes of water proton relaxation times. The second class (PARACEST) comprises a family of lanthanide-based paramagnetic compounds suitable for CEST imaging. The need for both types of MR agents is justified by efforts to utilize magnetic resonance imaging (MRI) to visualize fine structures in living tissue, and to increase the molecular specificity of MRI. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.
Journal of the American Chemical Society, 2014
Chemical exchange saturation transfer (CEST) agents are a new class of frequency-encoding MRI contrast agents with a great potential for molecular and cellular imaging. As for other established MRI contrast agents, the main drawback deals with their low sensitivity. The sensitivity issue may be tackled by increasing the number of exchanging protons involved in the transfer of saturated magnetization to the "bulk" water signal. Herein we show that the water molecules in the cytoplasm of red blood cells can be exploited as source of exchangeable protons provided that their chemical shift is properly shifted by the intracellular entrapment of a paramagnetic shift reagent. The sensitivity of this system is the highest displayed so far among CEST agents (less than 1 pM of cells), and the natural origin of this system makes it suitable for in vivo applications. The proposed Ln-loaded RBCs may be proposed as reporters of the blood volume in the tumor region. Communication pubs.acs.org/JACS
Magnetic Resonance in Medicine, 2012
A variety of (super)paramagnetic contrast agents are available for enhanced MR visualization of specific tissues, cells, or molecules. To develop alternative contrast agents without the presence of metal ions, liposomes were developed containing simple bioorganic and biodegradable compounds that produce diamagnetic chemical exchange saturation transfer MR contrast. This diamagnetic chemical exchange saturation transfer contrast is frequency-dependent, allowing the unique generation of “multicolor” images. The contrast can be turned on and off at will, and standard images do not show the presence of these agents. As an example, glycogen, L-arginine, and poly-L-lysine were encapsulated inside liposomes and injected intradermally into mice to image the lymphatic uptake of these liposomes. Using a frequency-dependent acquisition scheme, it is demonstrated that multicolor MRI can differentiate between different contrast particles in vivo following their homing to draining lymph nodes. Being nonmetallic and bioorganic, these diamagnetic chemical exchange saturation transfer liposomes form an attractive novel platform for multicolor imaging in vivo. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.
Investigative Radiology, 2004
Rationale and Objectives: Paramagnetic Ln-DOTAMGly complexes (Ln La, Lu, and Gd) are the prototypes of a novel class of contrast agents for magnetic resonance imaging based on chemical exchange saturation transfer (CEST). Their ability to reduce the water signal intensity depends on the interplay of several physicochemical properties of the agent and instrumental parameters. This study aims to identify possible routes for their optimization Methods: Saturation transfer (ST) has been measured in vitro at 7.05 T as a function of pH, temperature, and concentration of the agent. Results: Large saturation transfer effects have been observed upon irradiating the coordinated water protons (for Ln ϭ Pr, Nd, Eu, and Tb). The comparison of the results obtained by irradiating water versus amide protons allows the setup of ratiometric methods through which the ST response can be made independent on the concentration of the agent. Conclusions: The modulation of the magnetic properties along the lanthanide series allows an in-depth understanding of the determinants of ST effect and provides useful insights for the design of more efficient agents.
Off-resonance experiments and contrast agents to improve magnetic resonance imaging
Magnetic Resonance in Medicine, 1998
The effect of off-resonance irradiation on the water proton NMR signal intensity has been investigated as follows: (a) in the presence of a paramagnetic probe like manganese(l1); (b) in the presence of bovine serum albumin (BSA) and two gadolinium(lll) complexes, Gd-DTPA and Gd-BOPTA; (c) in the presence of cross-linked BSA and the two above-mentioned gadolinium(lll) complexes. The experimental data have been rationalized on the basis of the available theoretical models.
Structure-Relaxivity Relationships among Targeted MR Contrast Agents
European Journal of Inorganic Chemistry, 2012
Paramagnetic gadolinium(III) complexes are widely used to increase contrast in magnetic resonance (MR) images. Contrast enhancement depends on the concentration of the gadolinium complex and on its relaxivity, an inherent property of the complex. Increased relaxivity results in greater image contrast or the ability to detect the contrast agent at a lower concentration. Increasing relaxivity enables imaging of abundant molecular targets. Relaxivity depends on the structure of the complex, kinetics of inner-sphere and second sphere water exchange, and on the rotational dynamics of the molecule. The latter, and in some cases the former, properties of the complex change when it is bound to its target. All of these properties can be rationally tuned to enhance relaxivitry. In this Microreview we summarize our efforts in understanding and optimizing the relaxivity of contrast agents targeted to serum albumin and to fibrin.