Hexafluorobenzene: a Sensitive19F NMR Indicator of Tumor Oxygenation

Mason, Ralph P.; Rodbumrung, Watchara; Antich, Peter P.

doi:10.1002/(sici)1099-1492(199605)9:3<125::aid-nbm405>3.0.co;2-f

Cited by 109 publications

(88 citation statements)

References 40 publications

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“…emulsions into tumors, but this increases the volume Hexafluorobenzene has many virtues as a P 0 2 reporter considerably making it more invasive [206]. Investigators [173]. Symmetry provides a single narrow 19 F NMR signal have suggested that emulsification improves retention at the and the spin lattice relaxation rate is highly sensitive to site of injection.…”

Section: Fluorinatedp02 Reporter Moleculesmentioning

confidence: 92%

“…HFB exhibits remarkable lack tumors [169,170,[186][187][188][189][190][191][192][193][194][195][196][197][198][199][200][201][202]. of temperature dependence and the comparative error would Uptake and deposition of PFC emulsions in tumors is be 0.1 torr/°C [173].…”

Section: Fluorinatedp02 Reporter Moleculesmentioning

confidence: 99%

“…Symmetry provides a single narrow 19 F NMR signal have suggested that emulsification improves retention at the and the spin lattice relaxation rate is highly sensitive to site of injection. Direct injection of neat PFC has also been changes in P 0 2, yet minimally responsive to temperature used to investigate retinal oxygenation [207][208][209] and [173]. Prior to our applications of HFB to tumor oximetry cerebral oxygenation in the interstitial and ventricular spaces in vivo, several studies had examined the interaction of [210].…”

Section: Fluorinatedp02 Reporter Moleculesmentioning

confidence: 99%

“…Most into the center or periphery of a tumor using a very fine significantly, estimates of P 0 2 and modulation of tumor sharp tipped needle (32 gauge). Local P 0 2 measurements hypoxia are found to be consistent with, modified tumor indicated tumor heterogeneity [169,173]. The insertion of a response to irradiation [201]13.…”

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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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: 92%

Section: Fluorinatedp02 Reporter Moleculesmentioning

confidence: 99%

Section: Fluorinatedp02 Reporter Moleculesmentioning

confidence: 99%

Section: Fluorinatedp02 Reporter Moleculesmentioning

confidence: 99%

See 2 more Smart Citations

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

Mason¹

2005

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“…The blood oxygen level dependent (BOLD) effect 55 has been extensively used for functional MRI of the brain despite the relatively low sensitivity of effective T 2 to tissue oxygenation and dispersion of the data. Several NMR techniques for oxygen measurement were developed relying on exogenous fluorinated probes, including 19 F NMR spectroscopy/imaging using perfluorocarbon (PFC) emulsions 56,57 and fluorinated nitroimidazoles. 58 However, spin lattice relaxation rates of fluorinated probes may also depend on other physiological or histological parameters.…”

Section: Magnetic Resonance Approaches For In Vivo Oximetrymentioning

confidence: 99%