Improved Quantification of Islet Transplants by Magnetic Resonance Imaging With Resovist

Park, Ki-Soo; Lee, Han-Shin; Kim, Young-Seok; Kang, Tong Mook; Lee, Jung‐Hee; Joh, Jae‐Won; Kim, Jong Man

doi:10.1097/mpa.0b013e31821fd66a

Cited by 11 publications

(7 citation statements)

References 44 publications

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“…Based on these observations, we may validate the commercial use of SPIONs in clinics based on our experimental results even though a direct comparison may not be available. For clinical labeling of cells in MRI, commercialized SPIONs (Resovist ® , Schering, Germany) have been used at concentrations of 5∼25 ppm (µg/mL) depending on the patient's weight; 43,44 this concentration range is biologically safe based on our data from Figures 2 and 4. seM and TeM observations SEM and TEM images of each cell were obtained after the cytotoxicity test. Figure 5A shows the SEM images of L-929 cells treated with each SPION at a concentration of 500 ppm; the WST-8 assay indicates that the cells might be partly damaged at this concentration.…”

mentioning

confidence: 99%

Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups

Hong¹,

Lee²,

Lee³

et al. 2011

IJN

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Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely utilized for the diagnosis and therapy of specific diseases, as magnetic resonance imaging (MRI) contrast agents and drug-delivery carriers, due to their easy transportation to targeted areas by an external magnetic field. For such biomedical applications, SPIONs must have multifunctional characteristics, including optimized size and modified surface. However, the biofunctionality and biocompatibility of SPIONs with various surface functional groups of different sizes have yet to be elucidated clearly. Therefore, it is important to carefully monitor the cytotoxicity and genotoxicity of SPIONs that are surfaced-modified with various functional groups of different sizes. In this study, we evaluated SPIONs with diameters of approximately 10 nm and 100~150 nm, containing different surface functional groups. SPIONs were covered with −O − groups, so-called bare SPIONs. Following this, they were modified with three different functional groups – hydroxyl (−OH), carboxylic (−COOH), and amine (−NH 2 ) groups – by coating their surfaces with tetraethyl orthosilicate (TEOS), (3-aminopropyl)trimethoxysilane (APTMS), TEOS-APTMS, or citrate, which imparted different surface charges and sizes to the particles. The effects of SPIONs coated with these functional groups on mitochondrial activity, intracellular accumulation of reactive oxygen species, membrane integrity, and DNA stability in L-929 fibroblasts were determined by water-soluble tetrazolium, 2′,7′-dichlorodihydrofluorescein, lactate dehydrogenase, and comet assays, respectively. Our toxicological observations suggest that the functional groups and sizes of SPIONs are critical determinants of cellular responses, degrees of cytotoxicity and genotoxicity, and potential mechanisms of toxicity. Nanoparticles with various surface modifications and of different sizes induced slight, but possibly meaningful, changes in cell cytotoxicity and genotoxicity, which would be significantly valuable in further studies of bioconjugation and cell interaction for drug delivery, cell culture, and cancer-targeting applications.

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mentioning

confidence: 99%

Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups

Hong¹,

Lee²,

Lee³

et al. 2011

IJN

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“…Our results also indicate that MNPs rarely show genotoxicity below at 100 μg/mL, but more careful investigation is required when MNPs are treated at concentrations above 100 μg/mL. For clinical labeling of cells in MRI, commercialized SPIONs (Resovist ® , Schering, Germany) are currently used at concentrations of 5–25 μg/mL depending on the patient’s weight [40,41]; this concentration range is biologically safe based on our data from Figure 2, Figure 3 and Figure 4. Although only dextran-coated SPIONs are approved for human in vivo use by the Food and Drug Administration [42], several SPIONs with various physicochemical properties are in clinical trials and will be utilized for various biomedical applications in the near future [43].…”

Section: Resultsmentioning

confidence: 96%

Difference between Toxicities of Iron Oxide Magnetic Nanoparticles with Various Surface-Functional Groups against Human Normal Fibroblasts and Fibrosarcoma Cells

et al. 2013

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Recently, many nanomedical studies have been focused on magnetic nanoparticles (MNPs) because MNPs possess attractive properties for potential uses in imaging, drug delivery, and theranostics. MNPs must have optimized size as well as functionalized surface for such applications. However, careful cytotoxicity and genotoxicity assessments to ensure the biocompatibility and biosafety of MNPs are essential. In this study, Fe3O4 MNPs of different sizes (approximately 10 and 100–150 nm) were prepared with different functional groups, hydroxyl (–OH) and amine (–NH2) groups, by coating their surfaces with tetraethyl orthosilicate (TEOS), 3-aminopropyltrimethoxysilane (APTMS) or TEOS/APTMS. Differential cellular responses to those surface-functionalized MNPs were investigated in normal fibroblasts vs. fibrosarcoma cells. Following the characterization of MNP properties according to size, surface charge and functional groups, cellular responses to MNPs in normal fibroblasts and fibrosarcoma cells were determined by quantifying metabolic activity, membrane integrity, and DNA stability. While all MNPs induced just about 5% or less cytotoxicity and genotoxicity in fibrosarcoma cells at lower than 500 μg/mL, APTMS-coated MNPs resulted in greater than 10% toxicity against normal cells. Particularly, the genotoxicity of MNPs was dependent on their dose, size and surface charge, showing that positively charged (APTMS- or TEOS/APTMS-coated) MNPs induced appreciable DNA aberrations irrespective of cell type. Resultantly, smaller and positively charged (APTMS-coated) MNPs led to more severe toxicity in normal cells than their cancer counterparts. Although it was difficult to fully differentiate cellular responses to various MNPs between normal fibroblasts and their cancer counterparts, normal cells were shown to be more vulnerable to internalized MNPs than cancer cells. Our results suggest that functional groups and sizes of MNPs are critical determinants of degrees of cytotoxicity and genotoxicity, and potential mechanisms of toxicity.

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“…The toxicity of Resovist® for islets was weaker than that of Feridex® in an in vitro assay 54 . The lower toxicity was also confirmed by the Park group 55 . Ris and colleagues also compared three SPIOs, Resovist®, Endorem®, and Feridex®, in terms of their stability and function using rat syngeneic and xenogeneic (human to rat) intraportal transplant models, and found that Resovist® had better insulin-releasing ability and signal stability than Endorem® or Feridex®.…”

Section: Mrimentioning

confidence: 84%

Imaging of transplanted islets by positron emission tomography, magnetic resonance imaging, and ultrasonography

Sakata

Yoshimatsu

Tsuchiya

et al. 2013

Islets

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While islet transplantation is considered a useful therapeutic option for severe diabetes mellitus (DM), the outcome of this treatment remains unsatisfactory. This is largely due to the damage and loss of islets in the early transplant stage. Thus, it is important to monitor the condition of the transplanted islets, so that a treatment can be selected to rescue the islets from damage if needed. Recently, numerous trials have been performed to investigate the efficacy of different imaging modalities for visualizing transplanted islets. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are the most commonly used imaging modalities for this purpose. Some groups, including ours, have also tried to visualize transplanted islets by ultrasonography (US). In this review article, we discuss the recent progress in islet imaging.

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Improved Quantification of Islet Transplants by Magnetic Resonance Imaging With Resovist

Abstract: Islet transplant survival may be safely and accurately monitored using magnetic resonance imaging with the Resovist. We found in this study that pixel number may correlate more closely than the number of contrast spots with the number of islets transplanted.

Cited by 11 publications

References 44 publications

Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups

Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups

Difference between Toxicities of Iron Oxide Magnetic Nanoparticles with Various Surface-Functional Groups against Human Normal Fibroblasts and Fibrosarcoma Cells

Imaging of transplanted islets by positron emission tomography, magnetic resonance imaging, and ultrasonography

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