A Trimodal Imaging Platform for Tracking Viable Transplanted Pancreatic Islets In Vivo: F-19 MR, Fluorescence, and Bioluminescence Imaging

Gálisová, Andrea; Herynek, Vı́t; Swider, Edyta; Sticová, Eva; Patikova, Alzbeta; Kosinová, Lucie; Kříž, Jan; Hájek, Milan; Srinivas, Mangala; Jirák, Daniel

doi:10.1007/s11307-018-1270-3

Cited by 26 publications

(31 citation statements)

References 44 publications

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“…We observed a rapid decline in the in vivo fluorescence signal within the first days after administration. Previous animal model studies to have used other imaging probes report the dissociation of MR and fluorescence signals, a similar effect possibly caused by lysosomal degradation of fluorescent dyes 51,52 .…”

Section: Discussionmentioning

confidence: 82%

Glycogen as an advantageous polymer carrier in cancer theranostics: Straightforward in vivo evidence

Gálisová

Jirátová

Rabyk

et al. 2020

Sci Rep

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As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumourbearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment. The majority of anticancer drugs are highly toxic and adversely affect healthy cells due to a lack of specific targeting 1,2. Therefore, a safe drug delivery system capable of accumulating and providing controlled drug release at the tumour site is highly desirable. Nanoparticles represent a versatile carrier for drug delivery due to their ability to passively accumulate in solid tumours. This occurs via the enhanced permeability and retention (EPR) effect, a relatively universal phenomenon whereby nano-sized structures (up to approx. 200 nm in size) become entrapped in tumour tissue due to either leaky endothelia or aberrant tumour vessel architecture. Restricted or even completely absent lymphatic drainage in tumours limits the release and passive accumulation of compounds 3. Nanotherapeutic carrier can accumulate in tumours via the EPR effect without any targeting ligand 4-6. Their size above the renal threshold (molecular weight > ca 45 kDa/hydrodynamic diameter > 8 nm) leads to prolonged circulation in the bloodstream increasing the probability of accumulation at the target site 3. Importantly, polymers can control the release of drugs, being composed of a structure responsive to external stimuli, such as pH changes in acidic cancer-cell environments 7 , the presence of enzymes, and redox potential 8,9. Thus to minimise the drug release in the bloodstream and the cytotoxic effect on healthy cells 10-12. One limitation of nanoparticles is that they tend to opsonise, clearing quickly through the reticuloendothelial system in the liver and spleen 13. However, this can be mitigated by surface modification: for instance, grafting nanoparticles with poly(ethylene oxide) (PEO) (known also as poly(ethylene glycol)-PEG) is a well-established pr...

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Section: Discussionmentioning

confidence: 82%

Glycogen as an advantageous polymer carrier in cancer theranostics: Straightforward in vivo evidence

Gálisová

Jirátová

Rabyk

et al. 2020

Sci Rep

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“…Gálisová et al developed a PLGA-NP poly(lactic-co-glycolic acid) platform, wherein PLGA-NP poly(lactic-co-glycolic acid) encapsulated with perfluoro-15-crown-5-ether and the near-infrared fluorescent dye indocyanine green and obtained detailed information about localization, size, and viability of transplanted islets by multimodal imaging (Figure 3). 11 Recently, a new pancreatic β-cell probe, PiF (pancreatic islet fluorinated probe), was developed. This probe can not only image the islets in the pancreas but also monitor the intraportal transplanted islets by simple tail vein injection without the prelabeling of islets.…”

Section: Multimodality Imagingmentioning

confidence: 99%

“…Second, SPIO is highly sensitive but has low imaging specificity due to hypointense signal contents in the body; thus, it is difficult to quantify. 11 Third, SPIO is biodegradable and is easily affected by the surrounding internal environments. 12 The Küpffer cells in the liver decompose SPIO quickly, affecting the signal observation of the labeled islets.…”

Section: Magnetic Resonance Imaging (Mri)mentioning

confidence: 99%

<p>Islet Transplantation Imaging in vivo</p>

Zheng

Wang

Yang

et al. 2020

DMSO

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Although islet transplantation plays an effective and powerful role in the treatment of diabetes, a large amount of islet grafts are lost at an early stage due to instant bloodmediated inflammatory reactions, immune rejection, and β-cell toxicity resulting from immunosuppressive agents. Timely intervention based on the viability and function of the transplanted islets at an early stage is crucial. Various islet transplantation imaging techniques are available for monitoring the conditions of post-transplanted islets. Due to the development of various imaging modalities and the continuous study of contrast agents, noninvasive islet transplantation imaging in vivo has made great progress. The tracing and functional evaluation of transplanted islets in vivo have thus become possible. However, most studies on contrast agent and imaging modalities are limited to animal experiments, and long-term toxicity and stability need further evaluation. Accordingly, the clinical application of the current achievements still requires a large amount of effort. In this review, we discuss the contrast agents for MRI, SPECT/PET, BLI/FI, US, MPI, PAI, and multimodal imaging. We further summarize the advantages and limitations of various molecular imaging methods.

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“…MR imaging, on the other hand, has a very high spatial resolution and can accurately map the position of intracranial lesions [7]. Moreover, by labelling cells prior to administration with an appropriate contrast agent, such as iron oxide particles [8] or 19 Fbased tracking agents [9], MRI can be used to plot the biodistribution of the cells over time.…”

Section: Introductionmentioning

confidence: 99%

Assessing Human Embryonic Stem Cell-Derived Dopaminergic Neuron Progenitor Transplants Using Non-invasive Imaging Techniques

et al. 2020

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Purpose Human pluripotent stem cell (hPSC)-derived dopaminergic neuron progenitor cells (DAPCs) are a potential therapy for Parkinson’s disease (PD). However, their intracranial administration raises safety concerns including uncontrolled proliferation, migration and inflammation. Here, we apply a bimodal imaging approach to investigate the fate of DAPC transplants in the rat striatum. Procedures DAPCs co-expressing luciferase and ZsGreen or labelled with micron-sized particles of iron oxide (MPIOs) were transplanted in the striatum of RNU rats (n = 6 per group). DAPCs were tracked in vivo using bioluminescence and magnetic resonance (MR) imaging modalities. Results Transgene silencing in differentiating DAPCs accompanied with signal attenuation due to animal growth rendered the bioluminescence undetectable by week 2 post intrastriatal transplantation. However, MR imaging of MPIO-labelled DAPCs showed that transplanted cells remained at the site of injection for over 120 days. Post-mortem histological analysis of DAPC transplants demonstrated that labelling with either luciferase/ZsGreen or MPIOs did not affect the ability of cells to differentiate into mature dopaminergic neurons. Importantly, labelled cells did not elicit increased glial reactivity compared to non-labelled cells. Conclusions In summary, our findings support the transplantation of hPSC-derived DAPCs as a safe treatment for PD.

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A Trimodal Imaging Platform for Tracking Viable Transplanted Pancreatic Islets In Vivo: F-19 MR, Fluorescence, and Bioluminescence Imaging

Cited by 26 publications

References 44 publications

Glycogen as an advantageous polymer carrier in cancer theranostics: Straightforward in vivo evidence

Glycogen as an advantageous polymer carrier in cancer theranostics: Straightforward in vivo evidence

<p>Islet Transplantation Imaging in vivo</p>

Assessing Human Embryonic Stem Cell-Derived Dopaminergic Neuron Progenitor Transplants Using Non-invasive Imaging Techniques

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