Imaging Islets Labeled With Magnetic Nanoparticles at 1.5 Tesla

Tai, Joo Ho; Foster, Paula J.; Rosales, Alma; Feng, Biao; Hasilo, Craig; Martinez, Violetta; Ramadan, Soha S.; Snir, Jonatan; Melling, C.W. James; Dhanvantari, Savita; Rutt, Brian K.; White, David J.

doi:10.2337/db06-0393

Cited by 141 publications

(139 citation statements)

References 37 publications

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“…As cationic surfaces have been shown to facilitate cellular internalization [20,21], USPIO are often modified with polycationic cell permeating peptides (CPP) such as HIV transactivator (TAT) [22] or protamine [23]. Other transfection techniques, sometimes in concert with CPPs, are also used [24,25].…”

Section: Introductionmentioning

confidence: 99%

Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells

2008

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A promising new direction for contrast-enhanced magnetic resonance (MR) imaging involves tracking the migration and biodistribution of superparamagnetic iron oxide (SPIO)-labeled cells in vivo. Despite the large number of cell labeling studies that have been performed with SPIO particles of differing size and surface charge, it remains unclear which SPIO configuration provides optimal contrast in non-phagocytic cells. This is largely because contradictory findings have stemmed from the variability and imprecise control over surface charge, the general need and complexity of transfection and/or targeting agents, and the limited number of particle configurations examined in any given study. In the present study, we systematically evaluated the cellular uptake of SPIO in non-phagocytic T cells over a continuum of particle sizes ranging from 33 nm to nearly 1.5 μm, with precisely controlled surface properties, and without the need for transfection agents. SPIO labeling of T cells was analyzed by flow cytometry and contrast enhancement was determined by relaxometry. SPIO uptake was dose dependent and exhibited sigmoidal charge dependence, which was shown to saturate at different levels of functionalization. Efficient labeling of cells was observed for particles up to 300nm, however micron-sized particle uptake was limited. Our results show that an unconventional highly cationic particle configuration at 107 nm maximized MR contrast of T cells, outperforming the widely utilized USPIO (<50 nm).

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Section: Introductionmentioning

confidence: 99%

Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells

2008

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“…Targeting GLP-1R specifically expressed on the b-cells of the pancreatic islets offers an attractive alternative to methods using islets prelabeled with ultrasmall superparamagnetic iron oxide particles as described by Evgenov et al (7) and others (6,(16)(17)(18). Targeting a receptor, such as GLP-1R, may potentially offer higher specificity and does not require prelabeling of islets.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Imaging of Islet Transplants with ¹¹¹In-Exendin-3 SPECT/CT

et al. 2016

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Islet transplantation is a promising treatment for type 1 diabetic patients. However, there is acute as well as chronic loss of islets after transplantation. A noninvasive imaging method that could monitor islet mass might help to improve transplantation outcomes. In this study, islets were visualized after transplantation in a rat model with a dedicated small-animal SPECT scanner by targeting the glucagonlike peptide-1 receptor (GLP-1R), specifically expressed on β-cells, with 111 In-labeled exendin-3. Methods: Targeting of 111 Inexendin-3 to GLP-1R was tested in vitro on isolated islets of WAG/Rij rats. For in vivo evaluation, 400 or 800 islets were transplanted into the calf muscle of WAG/Rij rats (6-8 wk old). Four weeks after transplantation, SPECT/CT images were acquired 1 h after injection of 111 In-labeled exendin-3. After SPECT acquisition, the muscles containing the transplant were analyzed immunohistochemically and autoradiographically. Results: The binding assay, performed on isolated islets, showed a linear correlation between the number of islets and 111 In-exendin-3 accumulation (Pearson r 5 0.98). In vivo, a 1.70 ± 0.44-fold difference in tracer uptake between 400 and 800 transplanted islets was observed. Ex vivo analysis of the islet transplant showed colocalization of tracer accumulation on autoradiography, with insulin-positive cells and GLP-1R expression on immunohistochemistry. Conclusion: 111 In-exendin-3 accumulates specifically in the β-cells after islet transplantation and is a promising tracer for noninvasive monitoring of the islet mass. For type 1 diabetic patients with poor glycemic control, pancreatic islet transplantation is a promising but still experimental treatment. The standard transplantation procedure is infusion of pancreatic islets in the portal vein, where islets are trapped in the sinusoidal capillaries of the liver. Most patients become insulinindependent for more than 1 y after transplantation. However, insulin independency drops to approximately 10% 5 y after transplantation (1). Even though these insulin-dependent patients still profit from this treatment because instability of blood glucose levels and risk of hypoglycemia are reduced, further improvement of transplant survival and islet function is warranted, especially in view of the side effects of the immunosuppressive treatment that is required to prevent rejection of the transplanted islets (1-3).Current methods of monitoring islets after transplantation, such as measurement of hemoglobin A 1C , C-peptide, and insulin levels, provide only functional information and cannot accurately predict the number of surviving islets. Medical imaging methods may offer the possibility of monitoring the number of surviving islets after transplantation, potentially providing information (complementary to functional capacity) about the effect of interventions on transplantation outcome. This information might help to further improve this new therapeutic approach in order to achieve longerlasting insulin independency.Numerous st...

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“…Most applicable to a clinical setting are positron emission tomography (PET) and magnetic resonance imaging (MRI) [2][3][4]. Their medical potential is undoubted but, to date, only optical methods have provided the necessary spatial resolution to resolve individual islets [5].…”

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confidence: 99%

In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy

et al. 2009

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Aims/hypothesis Structural and functional imaging of the islets of Langerhans and the insulin-secreting beta cells represents a significant challenge and a long-lasting objective in diabetes research. In vivo microscopy offers a valuable insight into beta cell function but has severe limitations regarding sample labelling, imaging speed and depth, and was primarily performed on isolated islets lacking native innervations and vascularisation. This article introduces extended-focus optical coherence microscopy (xfOCM) to image murine pancreatic islets in their natural environment in situ, i.e. in vivo and in a label-free condition.Methods Ex vivo measurements on excised pancreases were performed and validated by standard immunohistochemistry to investigate the structures that can be observed with xfOCM. The influence of streptozotocin on the signature of the islets was investigated in a second step. Finally, xfOCM was applied to make measurements of the murine pancreas in situ and in vivo. Results xfOCM circumvents the fundamental physical limit that trades lateral resolution for depth of field, and achieves fast volumetric imaging with high resolution in all three dimensions. It allows label-free visualisation of pancreatic lobules, ducts, blood vessels and individual islets of Langerhans ex vivo and in vivo, and detects streptozotocin-induced islet destruction. Conclusions/interpretation Our results demonstrate the potential value of xfOCM in high-resolution in vivo studies to assess islet structure and function in animal models of diabetes, aiming towards its use in longitudinal studies of diabetes progression and islet transplants.

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Imaging Islets Labeled With Magnetic Nanoparticles at 1.5 Tesla

Cited by 141 publications

References 37 publications

Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells

Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells

Noninvasive Imaging of Islet Transplants with ¹¹¹In-Exendin-3 SPECT/CT

In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy

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Imaging Islets Labeled With Magnetic Nanoparticles at 1.5 Tesla

Cited by 141 publications

References 37 publications

Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells

Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells

Noninvasive Imaging of Islet Transplants with 111In-Exendin-3 SPECT/CT

In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy

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Noninvasive Imaging of Islet Transplants with ¹¹¹In-Exendin-3 SPECT/CT