Fluorocapsules for Improved Function, Immunoprotection, and Visualization of Cellular Therapeutics with MR, US, and CT Imaging

Barnett, Brad P.; Ruíz-Cabello, Jesús; Hota, Partha; Liddell, Robert P.; Walczak, Piotr; Howland, Valerie; Chacko, V. P.; Kraitchman, Dara L.; Arepally, Aravind; Bulte, Jeff W.M.

doi:10.1148/radiol.10092339

Cited by 97 publications

(76 citation statements)

References 33 publications

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“…Given that clinical trials ( 18,19 ) and nonhuman primate studies (20)(21)(22)(23) of engrafted encapsulated islets have been performed, the development of a clinically applicable method that enables noninvasive monitoring of the real-time delivery, tissue engraftment, and persistence of capsule integrity is highly desirable ( 24 ). To this end, capsules labeled with barium or bismuth sulfate ( 25 ), superparamagnetic iron oxide ( 26,27 ) perfl uorocarbons ( 28 ), or a combination of superparamagnetic iron oxide and gold nanoparticles ( 29 ) have been developed that allow monitoring of engraftment with MR imaging, fl uoroscopy or computed tomography (CT), and ultrasonography (US). However, microcapsules labeled with a positive MR contrast agent are preferred for better visualization of capsules engrafted into a transplantation site that appears dark on conventional MR images, such as the liver.…”

Section: Molecular Imaging: Gadolinium-gold Microcapsule Tracking Of mentioning

confidence: 99%

Trimodal Gadolinium-Gold Microcapsules Containing Pancreatic Islet Cells Restore Normoglycemia in Diabetic Mice and Can Be Tracked by Using US, CT, and Positive-Contrast MR Imaging

et al. 2011

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Purpose:To develop microcapsules that immunoprotect pancreatic islet cells for treatment of type I diabetes and enable multimodal cellular imaging of transplanted islet cells. Materials and Methods:All animal experiments were approved by the institutional animal care and use committee. Gold nanoparticles functionalized with DTDTPA (dithiolated diethylenetriaminepentaacetic acid):gadolinium chelates (GG) were coencapsulated with pancreatic islet cells by using protamine sulfate as a clinical-grade alginate cross linker. Conventional poly-Llysine-cross-linked microcapsules and unencapsulated islets were included as controls. The viability and glucose responsiveness of islet cells were assessed in vitro, and in vivo insulin (C-peptide) secretion was monitored for 6 weeks in (streptozotocin-induced) diabetic mice with ( n = 7) or without ( n = 8) intraabdominally engrafted islet cells. Five nondiabetic mice were included as controls. Differences between samples were calculated by using a nonparametric Wilcoxon Mann-Whitney method. To adjust for multiple comparisons, a signifi cance level of P , .01 was chosen. Generalized estimating equations were used to model cell function over time. Three mice with engrafted capsules were imaged in vivo with high-fi eld-strength (9.4-T) magnetic resonance (MR) imaging, micro-computed tomography (CT), and 40-MHz ultrasonography (US). Results:Encapsulated human pancreatic islets were functional in vitro for at least 2 weeks after encapsulation. Blood glucose levels in the diabetic mice transplanted with GG-labeled encapsulated mouse b TC6 insulinoma cells returned to normal within 1 week after transplantation, and normoglycemia was sustained for at least 6 weeks without the use of immunosuppressive drugs. GG microcapsules could be readily visualized with positive-contrast high-fi eld-strength MR imaging, micro-CT, and US both in vitro and in vivo. Conclusion:Cell encapsulation with GG provides a means of trimodal noninvasive tracking of engrafted cells.

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Section: Molecular Imaging: Gadolinium-gold Microcapsule Tracking Of mentioning

confidence: 99%

Trimodal Gadolinium-Gold Microcapsules Containing Pancreatic Islet Cells Restore Normoglycemia in Diabetic Mice and Can Be Tracked by Using US, CT, and Positive-Contrast MR Imaging

et al. 2011

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“…Placing PFC emulsions into alginate microspheres leads to spheres that are readily observed with 19 F MR imaging, US, and CT, increased in vitro insulin secretion, and enabled prolonged in vivo insulin secretion. 59,62 The strategy of incorporating contrast agents in the biomaterial may also allow for monitoring of mechanical stability in vivo. 55 Conceptually, microbead breakdown would result in dispersion of the contrast agent and altered signal intensity.…”

Section: Discussionmentioning

confidence: 99%

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

Appel

Ibarra

Somo

et al. 2016

Tissue Engineering Part C: Methods

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Transplantation of functional islets encapsulated in stable biomaterials has the potential to cure Type I diabetes. However, the success of these materials requires the ability to quantitatively evaluate their stability. Imaging techniques that enable monitoring of biomaterial performance are critical to further development in the field. Xray phase-contrast (XPC) imaging is an emerging class of X-ray techniques that have shown significant promise for imaging biomaterial and soft tissue structures. In this study, XPC imaging techniques are shown to enable three dimensional (3D) imaging and evaluation of islet volume, alginate hydrogel structure, and local soft tissue features ex vivo. Rat islets were encapsulated in sterile ultrapurified alginate systems produced using a highthroughput microfluidic system. The encapsulated islets were implanted in omentum pouches created in a rodent model of type 1 diabetes. Microbeads were imaged with XPC imaging before implantation and as whole tissue samples after explantation from the animals. XPC microcomputed tomography (mCT) was performed with systems using tube-based and synchrotron X-ray sources. Islets could be identified within alginate beads and the islet volume was quantified in the synchrotron-based mCT volumes. Omental adipose tissue could be distinguished from inflammatory regions resulting from implanted beads in harvested samples with both XPC imaging techniques. Individual beads and the local encapsulation response were observed and quantified using quantitative measurements, which showed good agreement with histology. The 3D structure of the microbeads could be characterized with XPC imaging and failed beads could also be identified. These results point to the substantial potential of XPC imaging as a tool for imaging biomaterials in small animal models and deliver a critical step toward in vivo imaging.

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“…Barnett and colleagues succeeded in detecting the location of transplanted islets in an animal model, using multimodal imaging modalities (including US) and alginate microcapsule formulations containing perfluorocarbons (19); however, few such studies have been published recently.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Ultrasonography Using a Nano/Microbubble Contrast Agent for Islet Transplantation

Sakata

Sax

Yoshimatsu

et al. 2015

American Journal of Transplantation

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Fluorocapsules for Improved Function, Immunoprotection, and Visualization of Cellular Therapeutics with MR, US, and CT Imaging

Cited by 97 publications

References 33 publications

Trimodal Gadolinium-Gold Microcapsules Containing Pancreatic Islet Cells Restore Normoglycemia in Diabetic Mice and Can Be Tracked by Using US, CT, and Positive-Contrast MR Imaging

Trimodal Gadolinium-Gold Microcapsules Containing Pancreatic Islet Cells Restore Normoglycemia in Diabetic Mice and Can Be Tracked by Using US, CT, and Positive-Contrast MR Imaging

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

Enhanced Ultrasonography Using a Nano/Microbubble Contrast Agent for Islet Transplantation

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