Improved route for the visualization of stem cells labeled with a Gd‐/Eu‐Chelate as dual (MRI and fluorescence) agent

Crich, Simonetta Geninatti; Biancone, Luigi; Cantaluppi, Vincenzo; Duò, Debora; Esposito, Giovanna; Russo, Simona; Camussi, Giovanni; Aime, Silvio

doi:10.1002/mrm.20072

Cited by 154 publications

(163 citation statements)

References 28 publications

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“…25 A recent study indicates no acute toxicity at very high intracellular dosage in stem cells, without long-term follow up. 36 In our experiments also the detectability of the CA trapped in muscle cells during a long period of time indicated the absence of acute toxicity.…”

Section: Toxicity Of the Casupporting

confidence: 66%

In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle

et al. 2005

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In vivo gene electrotransfer (ET) is a simple method of gene delivery in various tissues relying on the injection of plasmid DNA followed by application of electric pulses. Noninvasive tools are needed to evaluate the ET efficiency and the resulting tissue damages. In this study, we performed ET of rat tibialis muscle after injection of either a plasmid coding for luciferase or a contrast agent (CA) detected by using magnetic resonance imaging (MRI). Plasmid expression and CA intracellular trapped quantity were compared throughout the electric field intensity range 0-300 V/cm. Although the CA trapped quantity reflects only the electropermeabilization step, both measurements were correlated. MRI measurements gave easy access to tridimensional visualization of the labelled zones where the CA has been injected and the applied electric field had a value allowing permeabilization. We also performed MRI measurements of the water transverse relaxation time T2 as an indicator of tissue modification, and tested whether another CA specific for necrosis could be used to detect muscle necrosis at high electric field intensity. In conclusion, MRI measurements may bring multiparametric information upon the efficiency and tissue toxicity of an ET protocol by using a simple and safe CA.

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Section: Toxicity Of the Casupporting

confidence: 66%

In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle

et al. 2005

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“…No such problem was detected when electroporation pulses were used to load cells. 20 Despite possible acute toxic effects associated with this technique, it should probably be given preference in protocols aiming at quantitative estimations. Labeling dilution by cell division or by fusion with unlabeled muscle fibers is often put forward as a drawback of cell detection based on prior loading with a CA.…”

Section: Discussionmentioning

confidence: 99%

“…18 Although internalization pathways and long-term intracellular behavior of these molecules are not yet fully understood, it is well established that intracellular loading with these CAs is possible without significant impact on cell viability or function. 19,20 Accurate evaluation and monitoring of cell therapy protocols require a very sensitive technique, because of the small amount of injected therapeutic cells. For these reasons, SPIOs, which have very high T2 (and T2*) relaxivities, have been privileged over the past 10 years.…”

Section: Introductionmentioning

confidence: 99%

“…20,23,24 Grafted on Matrigel structures and subcutaneously implanted, endothelial progenitor cells labeled with Gd-HPDO3A were identified as hyperintensities 14 days after injection. 20 Plugged in mouse kidney, they were visible 24 h after injection. The authors demonstrated the possibility of using Gd chelates for cell monitoring, at least in tissues with low intrinsic NMR signal such as kidney and suggested that it might be tested in muscle.…”

Section: Introductionmentioning

confidence: 99%

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Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs

et al. 2009

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“…The NMRD profiles were measured in the range of magnetic fields from 0.00024 to 1.6 T (corresponding to 0.01-70 MHz proton Larmor frequencies). 44 The gadolinium concentration of the complex-conjugated MS2 solutions was measured by a relaxometric procedure (20 MHz and 25 °C). Three accurate determinations (each on 3 different samples of similar concentration, prepared by dilution) of the 1 H longitudinal water proton relaxation rate (R 1 obs ) were made at pH=6.9 on ca.…”

Section: Methodsmentioning

confidence: 99%

High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹

et al. 2008

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High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a five-fold increase in relaxivity, leading to a peak relaxivity (per Gd 3+ ion) of 41.6 mM -1 s -1 at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (i) there is facile diffusion of water to the interior of capsids and (ii) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2) and the NMRD fittings highlight the differences in the local motion for the internal (τ Rl = 440 ps) and external (τ Rl = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups. MANUSCRIPT TEXTMagnetic resonance imaging (MRI) is a routinely used noninvasive diagnostic technique, providing detailed images without the use of ionizing radiation. Although the resolution of MRI is excellent, its dynamic range is relatively narrow because of the limited variation in relaxation rates exhibited by water protons in vivo. When these differences are insufficient to distinguish between adjacent tissues, contrast enhancement is often achieved through the administration of synthetic agents that increase the water proton relaxation rates in accessible locations. Gadolinium complexes are the most often used for this purpose, with more than 10 million MRI studies being performed through their use each year. [2][3][4] The current commercially available Gd(III)-based contrast agents use poly(aminocarboxylate) chelates, and typically gram quantities of Gd must be injected to reach concentrations sufficient for usable contrast enhancement. However, this strategy is more difficult to apply to the specific imaging of biomarkers present in low (μM -nM) concentrations. To distinguish these sites from the background signal, targetable contrast agents will undoubtedly require significantly improved contrast enhancement efficiencies. 3,5 2 MRI contrast agents are commonly evaluated on the basis of relaxivity (r 1p ), which describes their ability to increase the longitudinal relaxation rate of nearby water molecule protons per millimolar concentration of agent applied. 6 Strategies for enhancing the relaxivity of contrast agents include increasing the number of bound water molecules (q), optimizing the water-residence time (τ M ) and increasing the rotational correlati...

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Improved route for the visualization of stem cells labeled with a Gd‐/Eu‐Chelate as dual (MRI and fluorescence) agent

Abstract: A simple labeling procedure of stem/progenitor cells based on the use of Gd-HPDO3A and Eu-HPDO3A, respectively, is described. The Gd-chelate acts as

Cited by 154 publications

References 28 publications

In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle

In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle

Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs

High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹

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Improved route for the visualization of stem cells labeled with a Gd‐/Eu‐Chelate as dual (MRI and fluorescence) agent

Abstract: A simple labeling procedure of stem/progenitor cells based on the use of Gd-HPDO3A and Eu-HPDO3A, respectively, is described. The Gd-chelate acts as

Cited by 154 publications

References 28 publications

In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle

In vivo NMR imaging evaluation of efficiency and toxicity of gene electrotransfer in rat muscle

Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs

High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents1

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High Relaxivity Gadolinium Hydroxypyridonate−Viral Capsid Conjugates: Nanosized MRI Contrast Agents¹