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>3.3.co;2-e

Cited by 17 publications

(21 citation statements)

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“…PFC has been incorporated in advantage of a high symmetry and a single 19 F NMR polyalginate beads for direct implantation at a site of interest resonance. While 15C5 has 20 equivalent fluorine atoms per [204,205]. We favor direct intratumoral (IT) injection of molecule and HFB has only 6, the difference in molecular neat PFC allowing any region of interest in a tumor to be weight (580 vs. 186) provides only 6% extra 19 F signal per interrogated immediately.…”

Section: Fluorinatedp02 Reporter Moleculesmentioning

confidence: 99%

“…For Therox F44E, we had problems achieving and 3 fluorine atoms per molecule, respectively (Table 7). standard calibration curves [235] and others have also Subsequent to administration, a washout period sufficient experienced unexpected values [205]. Specifically, N6th et for elimination of unbound marker is required, since there is al.…”

mentioning

confidence: 99%

“…Specifically, N6th et for elimination of unbound marker is required, since there is al. [205], found different calibration curves for the apparently no difference detectable in vivo in the chemical fluorohydrocarbon F44E in the pure state or when shifts of the parent molecule and the metabolites [150]. incorporated into polyalginate beads.…”

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confidence: 99%

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Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

Mason¹

2005

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Public reporting burden for this collection of information Is estimated to average 1 hour per response, Including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, ABSTRACT (Maximum 200 Words)Gene therapy holds great promise for treatment of breast cancer. In particular, clinical trials are underway to apply therapeutic genes related to pro-drug activation or to modulate the activity of oncogenes by blocking promoter sites. However, there are major problems in terms of assessing the delivery to target tissue, assessing the uniformity (versus heterogeneity) of biodistribution and determining whether the genes are expressed. We propose to design, evaluate and apply a novel approach to gene activity detection-specifically, using fluorinated substrates of P-galactosidase to reveal gene activity. Our prototype molecule PFONPG (para-fluoro-ortho-nitro-phenyl P3-D-galactopyranoside) is a direct analog of the traditional "yellow' biochemical indicator ONPG (ortho-nitro-phenyl 3-D-galactopyranoside). This shows useful MR characteristics, sensitivity to enzyme activity and ability to enter cells. We will synthesize analogs of this prototype to optimize MR and biological characteristics and explore the feasibility of tailoring the reporter to specific applications, e.g., exploiting P-gal activity to deliver specific physiological reporter molecules such as pH and potentially specific cytotoxic agents. The agents will be rigorously tested in solution, applied to cultured breast cancer cells and ultimately used to examine P-gal activity in vivo in transfected breast tumors in mice and rats. SUBJECT TERMS NUMBER OF PAGESGene therapy, fluorine NMR, P-galactosidase, pH 127 IntroductionGene therapy holds great promise for treatment of breast cancer (1, 2). In particular, clinical trials are underway to apply therapeutic genes related to pro-drug activation or modulation of the activity of oncogenes by blocking promoter sites. However, there are major problems in terms of assessing the delivery to target tissue, assessing the uniformity (versus heterogeneity) of biodistribution and determining whether the genes are expressed. We propose to design, evaluate and apply a novel approach to gene activity detection-specifically, using fluorinated substrates of P3-galactosidase to reveal gene activity. Our prototype molecule PFONPG (para-fluoro-ortho-nitro-phenyl [3-D-galactopyranoside) is a direct analog of the traditional "yellow' biochemical indicator ONPG (ortho-nitro-phenyl 13-D-galactopyranoside).This shows useful MR characteristics, sensitivity to enzyme activity ...

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Section: Fluorinatedp02 Reporter Moleculesmentioning

confidence: 99%

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Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

Mason¹

2005

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“…Indeed, DO is a critical parameter determining many aspects of cell function, including viability, metabolism and protein secretion (Dionne et al, 1989(Dionne et al, , 1991(Dionne et al, , 1993Mukundan et al, 1995;Papas et al, 1996Papas et al, , 1997Papas et al, , 1999b. Given this importance of oxygen, our laboratory, as well as others (McGovern et al, 1993;Noth et al, 1999), are developing NMRbased methods to measure DO concentration in tissue constructs by incorporating a perfluorocarbon emulsion in the hydrogel. Using the linear correlation between DO concentration and the inverse of the T 1 relaxation of 19 F (McGovern et al, 1993;Noth et al, 1999) the average oxygen concentration in a VOI can be measured.…”

Section: Introductionmentioning

confidence: 99%

“…Given this importance of oxygen, our laboratory, as well as others (McGovern et al, 1993;Noth et al, 1999), are developing NMRbased methods to measure DO concentration in tissue constructs by incorporating a perfluorocarbon emulsion in the hydrogel. Using the linear correlation between DO concentration and the inverse of the T 1 relaxation of 19 F (McGovern et al, 1993;Noth et al, 1999) the average oxygen concentration in a VOI can be measured. It should be noted that 19 F is the second most sensitive nucleus after 1 H and there is no significant amount of 19 F normally present in tissues, hence 19 F NMR spectroscopy is particularly suitable for constructs in NMR-compatible bioreactors and in vivo situations.…”

Section: Introductionmentioning

confidence: 99%

Modeling of encapsulated cell systems

Gross

Constantinidis

Sambanis

2007

Journal of Theoretical Biology

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Tissue engineered substitutes consisting of cells in biocompatible materials undergo remodeling with time as a result of cell growth and death processes. With inert matrices that do not directly influence cell growth, remodeling is driven mainly by the concentration of dissolved oxygen (DO). Insulinsecreting cell lines encapsulated in alginate-based beads and used as a pancreatic substitute represent such a case. Beads undergo remodeling with time so that an initially homogeneous distribution of cells is eventually replaced by a dense peripheral ring of primarily viable cells, whereas inner cells are mostly necrotic. This paper develops and analyzes a mathematical model of an encapsulated cell system of spherical geometry that tracks the viable and dead cell densities and the concentration of DO within the construct as functions of radial position and time. Model simulations are compared with experimental histology data on cell distribution. Correlations are then developed between the average intrabead DO concentration (AIDO) and the total viable cell number, as well as between AIDO and the radial cell and DO distributions in beads. As AIDO can be measured experimentally by incorporating a perfluorocarbon emulsion in the beads and acquiring 19 F nuclear magnetic resonance (NMR) spectroscopic data, these correlations can be used to track the remodeling that occurs in the construct in vitro and potentially in vivo. The usefulness of mathematical models in describing the dynamic changes that occur in tissue constructs with time, and the value of these models at obtaining additional information on the system when used interactively with experimental measurements, are discussed.

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Immunoisolation of transplants by entrapment in¹⁹F‐labelled alginate gels: production, biocompatibility, stability, and long‐term monitoring of functional integrity

Hillgärtner

Zimmermann

Mimietz

et al. 1999

Mat.‐wiss. u. Werkstofftech.

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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 17 publications

References 0 publications

Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

Modeling of encapsulated cell systems

Immunoisolation of transplants by entrapment in¹⁹F‐labelled alginate gels: production, biocompatibility, stability, and long‐term monitoring of functional integrity

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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 17 publications

References 0 publications

Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

Breast Cancer Gene Therapy: Development of Novel Non-Invasive Magnetic Resonance Assay to Optimize Efficacy

Modeling of encapsulated cell systems

Immunoisolation of transplants by entrapment in19F‐labelled alginate gels: production, biocompatibility, stability, and long‐term monitoring of functional integrity

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Immunoisolation of transplants by entrapment in¹⁹F‐labelled alginate gels: production, biocompatibility, stability, and long‐term monitoring of functional integrity