scholarly journals Water Diffusion Modulates the CEST Effect on Tb(III)-Mesoporous Silica Probes

2020 ◽  
Vol 6 (3) ◽  
pp. 38
Author(s):  
Fabio Carniato ◽  
Giuseppe Ferrauto ◽  
Mónica Muñoz-Úbeda ◽  
Lorenzo Tei

The anchoring of lanthanide(III) chelates on the surface of mesoporous silica nanoparticles (MSNs) allowed their investigation as magnetic resonance imaging (MRI) and chemical exchange saturation transfer (CEST) contrast agents. Since their efficiency is strongly related to the interaction occurring between Ln-chelates and “bulk” water, an estimation of the water diffusion inside MSNs channels is very relevant. Herein, a method based on the exploitation of the CEST properties of TbDO3A-MSNs was applied to evaluate the effect of water diffusion inside MSN channels. Two MSNs, namely MCM-41 and SBA-15, with different pores size distributions were functionalized with TbDO3A-like chelates and polyethylene glycol (PEG) molecules and characterized by HR-TEM microscopy, IR spectroscopy, N2 physisorption, and thermogravimetric analysis (TGA). The different distribution of Tb-complexes in the two systems, mainly on the external surface in case of MCM-41 or inside the internal pores for SBA-15, resulted in variable CEST efficiency. Since water molecules diffuse slowly inside silica channels, the CEST effect of the LnDO3A-SBA-15 system was found to be one order of magnitude lower than in the case of TbDO3A-MCM-41. The latter system reaches an excellent sensitivity of ca. 55 ± 5 μM, which is useful for future theranostic or imaging applications.

Nanoscale ◽  
2014 ◽  
Vol 6 (16) ◽  
pp. 9604-9607 ◽  
Author(s):  
Giuseppe Ferrauto ◽  
Fabio Carniato ◽  
Lorenzo Tei ◽  
He Hu ◽  
Silvio Aime ◽  
...  

LnIII–DO3A complexes anchored to MCM-41 mesoporous silica nanoparticles induce a strong paramagnetic shift of proximate silanol protons behaving as highly sensitive chemical exchange saturation transfer (CEST) MRI nanoprobes.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1655.3-1656
Author(s):  
P. Sewerin ◽  
D. Abrar ◽  
M. Frenken ◽  
X. Baraliakos ◽  
M. Schneider ◽  
...  

Background:To evaluate the glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVD) in patients with ankylosing spondylitis (AS) using GAG chemical exchange saturation transfer (gagCEST).Objectives:Does local GAG content in non-degenerative IVDs measured by gagCEST MRI differs between AS patients and HC?Methods:195 lumbar IVD of 15 patients with AS (mean age 50 ±10 years) and 25 healthy control patients (HC) were prospectively examined with 3 T magnetic resonance imaging (MRI). MRI protocol contained morphological T2 weighted (T2w) images to grade IVD according to the Pfirrmann classification and biochemical imaging with gagCEST to calculate a region of interest (ROI) of the nucleus pulposus (NP) and annulus fibrosus (AF). Prior to statistical testing of gagCEST effects in patients and HC, IVD were classified according to Pfirrmann.Results:Significantly lower gagCEST values of NP and AF were found in non-degenerative IVD (Pfirrmann 1 and 2) of AS patients compared to HC (NP: 1.88 % ±1.21% vs. 3.38 % ±1.71%; p<0.01; confidence interval (CI): 0.89%/2.11%. AF: 1.11 % ± 1.07 % vs. 1.96 %± 1.23 %; p<0.01; CI 0.39%/1.3%).Conclusion:GagCEST analysis of morphologically non-degenerative IVDs in T2w images showed significantly lower GAG values in patients with AS in the NP and AF compared to HC. Our results potentially allow for the detection of GAG loss prior to morphological degeneration.Figure 1.Comparison of morphological T2 weighted (T2w) images to grade IVD according to the Pfirrmann classification and biochemical imaging with gagCEST between HC (A and C) and AS patients (B and D) showing significant lower GAG levels in AS patients.Disclosure of Interests:Philipp Sewerin Grant/research support from: AbbVie Deutschland GmbH & Co. KGBristol-Myers Squibb Celgene GmbHLilly Deutschland GmbHNovartis Pharma GmbH Pfizer Deutschland GmbHRheumazentrum Rhein-Ruhr, Consultant of: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Speakers bureau: AMGEN GmbH AbbVie Deutschland GmbH & Co. KG Biogen GmbHBristol-Myers Squibb Celgene GmbH Chugai Pharma arketing Ltd. / Chugai Europe GmbHHexal Pharma Janssen-CilagGmbH Johnson & Johnson Deutschland GmbHLilly Deutschland GmbH / Lilly Europe / Lilly Global Novartis Pharma GmbH Pfizer Deutschland GmbH Roche Pharma Rheumazentrum Rhein-Ruhr Sanofi-Genzyme Deutschland GmbH Swedish Orphan Biovitrum GmbH UCB Pharma GmbH, Daniel Abrar: None declared, Miriam Frenken: None declared, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Matthias Schneider Grant/research support from: GSK, UCB, Abbvie, Consultant of: Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, Speakers bureau: Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, Benedikt Ostendorf: None declared, Christoph Schleich: None declared


2021 ◽  
Vol 118 (46) ◽  
pp. e2115113118
Author(s):  
Ved P. Tiwari ◽  
Yuki Toyama ◽  
Debajyoti De ◽  
Lewis E. Kay ◽  
Pramodh Vallurupalli

Conformational dynamics play critical roles in protein folding, misfolding, function, misfunction, and aggregation. While detecting and studying the different conformational states populated by protein molecules on their free energy surfaces (FESs) remain a challenge, NMR spectroscopy has emerged as an invaluable experimental tool to explore the FES of a protein, as conformational dynamics can be probed at atomic resolution over a wide range of timescales. Here, we use chemical exchange saturation transfer (CEST) to detect “invisible” minor states on the energy landscape of the A39G mutant FF domain that exhibited “two-state” folding kinetics in traditional experiments. Although CEST has mostly been limited to studies of processes with rates between ∼5 to 300 s−1 involving sparse states with populations as low as ∼1%, we show that the line broadening that is often associated with minor state dips in CEST profiles can be exploited to inform on additional conformers, with lifetimes an order of magnitude shorter and populations close to 10-fold smaller than what typically is characterized. Our analysis of CEST profiles that exploits the minor state linewidths of the 71-residue A39G FF domain establishes a folding mechanism that can be described in terms of a four-state exchange process between interconverting states spanning over two orders of magnitude in timescale from ∼100 to ∼15,000 μs. A similar folding scheme is established for the wild-type domain as well. The study shows that the folding of this small domain proceeds through a pair of sparse, partially structured intermediates via two discrete pathways on a volcano-shaped FES.


2015 ◽  
Vol 17 (5) ◽  
pp. 3525-3533 ◽  
Author(s):  
Gaurav Jha ◽  
Anoop N. ◽  
Abdur Rahaman ◽  
Moloy Sarkar

A nitrobenzoxadiazole (NBD) anchored mesoporous silica-based system has been designed and developed for the selective detection of fluoride in aqueous medium.


2005 ◽  
Vol 127 (9) ◽  
pp. 3057-3068 ◽  
Author(s):  
Julien Trébosc ◽  
Jerzy W. Wiench ◽  
Seong Huh ◽  
Victor S.-Y. Lin ◽  
Marek Pruski

Author(s):  
Dario Livio Longo ◽  
Pietro Irrera ◽  
Lorena Consolino ◽  
Phillip Zhe Sun ◽  
Michael T. McMahon

AbstractMagnetic Resonance Imaging (MRI) has been actively explored in the last several decades for assessing renal function by providing several physiological information, including glomerular filtration rate, renal plasma flow, tissue oxygenation and water diffusion. Within MRI, the developing field of chemical exchange saturation transfer (CEST) has potential to provide further functional information for diagnosing kidney diseases. Both endogenous produced molecules as well as exogenously administered CEST agents have been exploited for providing functional information related to kidney diseases in preclinical studies. In particular, CEST MRI has been exploited for assessing the acid-base homeostasis in the kidney and for monitoring pH changes in several disease models. This review summarizes several CEST MRI procedures for assessing kidney functionality and pH, for monitoring renal pH changes in different kidney injury models and for evaluating renal allograft rejection.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.


Cephalalgia ◽  
2015 ◽  
Vol 36 (3) ◽  
pp. 279-283 ◽  
Author(s):  
Jakob Udby Blicher ◽  
Anna Tietze ◽  
Manus J Donahue ◽  
Seth A Smith ◽  
Leif Østergaard

Introduction To investigate tissue flow disturbance and hypoxia during migraine aura, we studied a case of familial hemiplegic migraine (FHM) using novel magnetic resonance imaging (MRI) techniques. Case results A 44-year-old male was admitted with suspected stroke because of confusion and aphasia. Initial gadolinium-based perfusion MRI showed a decrease in cerebral blood flow and an increase in capillary flow disturbances within the left hemisphere. Later during the prolonged aura phase, chemical exchange saturation transfer MRI indicated a drop in pH in the affected area. The patient was diagnosed with an R908Q mutation in the ATP1A2 gene causing FHM type 2. Discussion During prolonged aura in FHM, MRI shows reduced CBF, capillary flow disturbances and a possible pH drop that could indicate tissue hypoxia.


The Analyst ◽  
2014 ◽  
Vol 139 (11) ◽  
pp. 2687-2690 ◽  
Author(s):  
Dario Livio Longo ◽  
Enza Di Gregorio ◽  
Riccardo Abategiovanni ◽  
Alberto Ceccon ◽  
Michael Assfalg ◽  
...  

In this communication, we report that protein remodeling processes, such as aggregation, unfolding and interaction with lipid membranes, may be investigated by magnetic resonance imaging (MRI) through the CEST mechanism.


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