In vivo determination of tumor oxygenation during growth and in response to carbogen breathing using 15C5-loaded alginate capsules as fluorine-19 magnetic resonance imaging oxygen sensors

Nöth, Ulrike; Rodrigues, L. M.; Robinson, Simon P.; Jork, Anette; Zimmermann, U.; Newell, Barry; Griffiths, John R.

doi:10.1016/j.ijrobp.2004.07.671

Cited by 30 publications

(41 citation statements)

References 40 publications

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“…Although our incorporation of PFCs in alginate microcapsules did not show a statistically signifi cant increase in the viability of encapsulated cells in vitro, insulin secretion was found to be improved. This enhanced cell function is likely the result of an increased oxygen concentration within the capsules, which can be measured at 19 F MR imaging ( 29 ). For clinical procedures, such as islet cell transplantation, this is vital because these capsules with PFC reservoirs could We have demonstrated the ability to depict fl uorocapsules with clinical US, CT, and MR imagers.…”

Section: Molecular Imaging: Multimodality Imaging Of Perfl Uorocarbonmentioning

confidence: 99%

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

Barnett¹,

Ruíz-Cabello²,

Hota

et al. 2011

Radiology

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Purpose:To develop novel immunoprotective alginate microcapsule formulations containing perfl uorocarbons (PFCs) that may increase cell function, provide immunoprotection for xenografted cells, and simultaneously enable multimodality imaging. Materials and Methods:All animal experiments were approved by an Institutional Animal Care and Use Committee. Cadaveric human islet cells were encapsulated with alginate, poly-L -lysine, and perfl uorooctyl bromide (PFOB) or perfl uoropolyether (PFPE).In vitro viability and the glucose-stimulation index for insulin were determined over the course of 2 weeks and analyzed by using a cross-sectional time series regression model. [MR] imaging) detection was determined for fl uorocapsules embedded in gel phantoms. C57BL/6 mice intraperitoneally receiving 6000 PFOB-labeled ( n = 6) or 6000 PFPE-labeled ( n = 6) islet-containing fl uorocapsules and control mice intraperitoneally receiving 6000 PFOBlabeled ( n = 6) or 6000 PFPE-labeled ( n = 6) fl uorocapsules without islets were monitored for human C-peptide (insulin) secretion during a period of 55 days. Mice underwent 19 F MR imaging at 9.4 T and micro-CT. Swine ( n = 2) receiving 9000 PFOB capsules through renal artery catheterization were imaged with a clinical multidetector CT scanner. Signal intensity was evaluated by using a paired t test.

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Section: Molecular Imaging: Multimodality Imaging Of Perfl Uorocarbonmentioning

confidence: 99%

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

Barnett¹,

Ruíz-Cabello²,

Hota

et al. 2011

Radiology

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“…[17] Similarly, Nöth et al reported that during the first few days following GH3 tumor homogenate injection the tumor pO 2 levels increased rapidly, then reached a plateau, and then the pO 2 level readily decreased. [18] These findings were supplemented by clinical measurements using polarographic needle electrodes in hundreds of patients, which showed increasing tumor hypoxic fraction with increasing tumor volume. [19] The relationship between the extent of tumor hypoxia and tumor volume is conceptually illustrated in Fig.…”

Section: Phenomena Of Tumor Hypoxiamentioning

confidence: 96%

“…[7,8] Commonly used exogenous surrogate hypoxia markers are compounds that are bioreducible within hypoxic cells, such as pimonidazole, [9] for which a commercial fluorescent antibody is available to reveal its microscopic distribution within the tumor. Positron emission tomography (PET) and single photon emission computed tomography are used to image exogenous hypoxia markers labeled with radiotracers, such as the widely used 18 F-fluoromisonidazole ( 18 F-MISO) [10,11] and the clinically validated 64 Cu-labeled agents [e.g., 64 Cu-diacetyl-bis(N 4 -methylthiosemicarbazonate) ( 64 Cu-ATSM)]. [12] Fig.…”

Section: Phenomena Of Tumor Hypoxiamentioning

confidence: 99%

“…[12] Fig. 1 shows the structures and bioreduction mechanisms of 18 F-MISO and 64 Cu-ATSM. Magnetic resonance spectroscopy of surrogate markers such as lactate, a metabolic product of anaerobic glycolysis, [13] or the evaluation of the tumor blood perfusion with dynamic contrast-enhanced magnetic resonance imaging has been used to noninvasively probe tumor hypoxia.…”

Section: Phenomena Of Tumor Hypoxiamentioning

confidence: 99%

“…Most of the patients could be escalated to 72 Gy while observing dose constraints to normal tissues. [58] Although this registered study includes an 18 F-HX4 imaging component, no report was found on how the hypoxia scan was used in clinical decisions. Table 1 summarizes the clinically investigated PET imaging agents for tumor hypoxia, metabolism and proliferation, and the dose escalation clinical trials using these agents.…”

Section: Biologic and Therapeutic Consequences Of Tumor Hypoxiamentioning

confidence: 99%

See 2 more Smart Citations

Targeting Tumor Hypoxia in Radiotherapy: A Brief Review of Historical Background and Recent Progress

Zhang¹,

Zhou²,

Zhao³

et al. 2016

ERHM

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Tumor hypoxia is a physiologic barrier to radiotherapy and anti-tumor drug delivery. Numerous efforts have been made to overcome this barrier and to improve therapeutic outcomes. Strategies for targeting tumor hypoxia have included chemical radiosensitizers and hyperthermia, followed by combined synergic therapeutic modalities. Clinical hypoxia measurements and the development of molecular imaging agents prompted trials on dose escalation in external beam radiotherapy, which takes advantage of contemporary sophisticated radiation dose delivery techniques. Increases in our understanding of hypoxia-induced biological pathways have led to the investigation of various hypoxia targeting drugs. Radiolabeled hypoxia targeting drugs deliver radionuclides into hypoxic tumor cells and achieve highly localized cell death. In this manuscript, we briefly review the methods of targeting tumor hypoxia in radiotherapy. These include image guided dose escalation in external beam radiotherapy, radiosensitizers, and radiolabeled agents targeting hypoxia pathways and the receptors on hypoxic tumor cells. Our current understanding of tumor hypoxia is the culmination of the collective efforts of generations of researchers. New frontiers are continuing to expand, as new discoveries are being made on both the macroscopic and molecular levels.

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Monitoring of dissolved oxygen and cellular bioenergetics within a pancreatic substitute

Gross

Long

Constantinidis

et al. 2007

Biotech & Bioengineering

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This work investigated the use of nuclear magnetic resonance (NMR) spectroscopy in combination with a mathematical model of an encapsulated cell system as a method for rapidly assessing the status of a pancreatic substitute. To validate this method, an in vitro experiment was performed in which the encapsulated cells were perfused in an NMR-compatible system and the dissolved oxygen (DO) concentration of the perfusing medium was lowered from 0.20 to 0.05 mM, then returned to 0.20 mM in a stepwise fashion. The cellular metabolic activity and bioenergetics were evaluated by measuring the oxygen consumption rate (via DO sensors) and nucleotide triphosphate levels (via (31)P NMR). By incorporating a perfluorocarbon emulsion into the alginate beads, the cellular oxygenation state was monitored by measuring the average intrabead DO (AIDO) concentration by (19)F NMR. The in vitro measurements were then compared with model predictions based on the measured external DO concentration and time. Model-predicted cell growth and AIDO closely matched the experimentally acquired data. As the DO concentrations both external to and within the pancreatic substitute are needed to apply this methodology in vivo, the feasibility of measuring the DO concentration from two distinct bead populations implanted in the peritoneal cavity of mice was established. It is concluded that PFC incorporation and (19)F NMR measurements, in combination with a mechanistic model of the encapsulated system, allow the tracking of the state of a pancreatic substitute in vitro and potentially in vivo.

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In vivo determination of tumor oxygenation during growth and in response to carbogen breathing using 15C5-loaded alginate capsules as fluorine-19 magnetic resonance imaging oxygen sensors

Cited by 30 publications

References 40 publications

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

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

Targeting Tumor Hypoxia in Radiotherapy: A Brief Review of Historical Background and Recent Progress

Monitoring of dissolved oxygen and cellular bioenergetics within a pancreatic substitute

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