19F-MRI in vivo determination of the partial oxygen pressure in perfluorocarbon-loaded alginate capsules implanted into the peritoneal cavity and different tissues

Nöth, Ulrike; Gröhn, Patrik; Jork, Anette; Zimmermann, U.; Haase, Axel; Lutz, Joachim

doi:10.1002/(sici)1522-2594(199912)42:6<1039::aid-mrm8>3.0.co;2-n

Cited by 56 publications

(47 citation statements)

References 37 publications

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“…The device equipped with a power supply system for electrohydrolysis of water molecules to hydrogen and oxygen may make a BAP complex and bulky and provoke additional biocompatibility issues (micro-gas bubble development, material-tissue interactions) when transplanted in the body. The introduction of perfluorocarbon emulsion with high oxygen solubility into alginate beads, which was originally attempted to monitor the capsules in vivo by 19 F nuclear magnetic resonance (NMR) after transplantation, 21,22 could be another option to increase partial oxygen tension inside the beads. The level stability of the emulsion and cell toxicity in the capsule, however, need to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Effect of Cross-Linked Hemoglobin on Functionality and Viability of Microencapsulated Pancreatic Islets

2002

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Of many obstacles involved in developing a bioartificial pancreas, which consists of encapsulated and physically immunoprotected islets, for long-term implantation in insulin-dependent diabetic patients, the impaired functionality and decreasing viability of encapsulated islets over time are critical factors in determining the size and longevity of the implant. These factors are closely associated with short oxygen supply to the encaged islets from the implant site. To facilitate oxygen transport to islets in the capsules, we coencapsulated hemoglobin cross-linked with difunctional polyethylene glycol (Hb-conjugate, Hb-C) which is large in size (>100 kDa), thus preventing diffusional loss through the immunoprotecting membrane. The coencapsulation of Hb-C with islets in alginate-poly-L-lysine microcapsules by dissolving Hb-C in an islet-suspended alginate solution at a concentration of 0.25 mM improved the insulin secretion and viability of the islets. At week 0, the islets, coencapsulated with Hb-C, cultured at P(O2) = 40 mmHg (assumed oxygen partial pressure in the most common implant site, the peritoneal cavity), secreted 200% more insulin compared with the control islets without Hb-C at glucose concentrations of both 100 and 300 mg/dL. The Hb-C effect became more significant with time at higher glucose concentrations. After culturing the islets for 8 weeks at 40 mmHg, the insulin secretion was enhanced 200 and 550% at glucose concentrations of 100 and 300 mg/dL as compared with the control, respectively. The results were closely associated with improved viability and suggest that the introduction of Hb-C is an effective approach to maintaining the oxygen supply to encapsulated islets. In addition, Hb-C coencapsulation with pancreatic islets may (1) provide a partial clue to reducing the large size of the biohybrid artificial pancreas, (2) lead to a reduced need for pancreas donation, and (3) prolong the longevity of the biohybrid artificial pancreas in the body.

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Section: Introductionmentioning

confidence: 99%

Effect of Cross-Linked Hemoglobin on Functionality and Viability of Microencapsulated Pancreatic Islets

2002

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“…It was also discovered that these compounds exhibited a unique property: their longitudinal relaxation time (R 1 ) varies linearly with the partial pressure of O 2 to which they were exposed (10). This created an impetus for further studies and resulted in a variety of techniques to noninvasively map the oxygen concentration in tumors (12,13,22), heart (23), lungs (24,25), and liver (26). Other studies used perfluorocarbons for general imaging of various organs, including the bowel (11,27).…”

Section: Discussionmentioning

confidence: 99%

“…To overcome the inherently low signal available with fluorine CMR, earlier reports used some combination of high field strengths (12,26,30), large doses (∼50% of blood volume replaced) (11), and/or long scan times, all of which compromise clinical imaging applications. On the contrary, the current demonstration of fluorine angiography utilized far smaller doses of nanoparticles that would be much more practical for clinical application, especially under conditions of steady state imaging.…”

Section: Discussionmentioning

confidence: 99%

Fluorine Cardiovascular Magnetic Resonance Angiography In Vivo at 1.5 T with Perfluorocarbon Nanoparticle Contrast Agents

Neubauer

Caruthers

Hockett

et al. 2007

J. of Cardiovascular Magnetic Resonance

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While the current gold standard for coronary imaging is X-ray angiography, evidence is accumulating that it may not be the most sensitive technique for detecting unstable plaque. Other imaging modalities, such as cardiovascular magnetic resonance (CMR), can be used for plaque characterization, but suffer from long scan and reconstruction times for determining regions of stenosis. We have developed an intravascular fluorinated contrast agent that can be used for angiography with cardiovascular magnetic resosnace at clinical field strengths (1.5 T). This liquid perfluorocarbon nanoparticle contains a high concentration of fluorine atoms that can be used to generate contrast on 19F MR images without any competing background signal from surrounding tissues. By using a perfluorocarbon with 20 equivalent fluorine molecules, custom-built RF coils, a modified clinical scanner, and an efficient steady-state free procession sequence, we demonstrate the use of this agent for angiography of small vessels in vitro, ex vivo, and in vivo. The surprisingly high signal generated with very short scan times and low doses of perfluorocarbon indicates that this technique may be useful in clinical settings when coupled with advanced imaging strategies.

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“…They cannot be identified by macrophages and do not initiate an immune response in the body. As they are large molecules and not ingested by tumor macrophages, they tend to be sequestrated at the implantation site for all practical purposes [75]. Oxygen can dissolve into the alginate layer and reach in to the PFC.…”

Section: Magnetic Resonance (Mr) Techniquesmentioning

confidence: 99%

Advances in methods for assessing tumor hypoxia in vivo: Implications for treatment planning

Davda

Bezabeh

2006

Cancer Metastasis Rev

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Tumor hypoxia and its downstream effects have remained of considerable interest for decades due to its negative impact on response to various cancer therapies and promotion of metastasis. Diagnosing hypoxia non-invasively can provide a significant advancement in cancer treatment and is the dire necessity for implementing specific targeted therapies now emerging to treat different aspects of cancer. A variety of techniques are being proposed to do so. However, none of them has yet been established in the clinical arena. This review summarizes the methods currently available to assess tumor hypoxia in vivo and their respective advantages and shortcomings. It also points out the impedances that need to be overcome to establish any particular method in the clinic, along with a broad overview of requirements for further advancement in this sphere of cancer research.

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19F-MRI in vivo determination of the partial oxygen pressure in perfluorocarbon-loaded alginate capsules implanted into the peritoneal cavity and different tissues

Cited by 56 publications

References 37 publications

Effect of Cross-Linked Hemoglobin on Functionality and Viability of Microencapsulated Pancreatic Islets

Effect of Cross-Linked Hemoglobin on Functionality and Viability of Microencapsulated Pancreatic Islets

Fluorine Cardiovascular Magnetic Resonance Angiography In Vivo at 1.5 T with Perfluorocarbon Nanoparticle Contrast Agents

Advances in methods for assessing tumor hypoxia in vivo: Implications for treatment planning

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