GdDO3NI, a nitroimidazole-based T 1 MRI contrast agent for imaging tumor hypoxia in vivo Topical Issue on Metal-Based MRI Contrast Agents. Guest editor

Valerie C. Pierre

Praveen K. Gulaka, Federico Rojas-Quijano, Zoltan Kovacs, Ralph P. Mason, A. Dean Sherry, Vikram D. Kodibagkar

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Tumor hypoxia is known to affect sensitivity to radiotherapy and promote development of metastases; therefore, the ability to image tumor hypoxia in vivo could provide useful prognostic information and help tailor therapy. We previously demonstrated in vitro evidence for selective accumulation of a gadolinium tetraazacyclododecanetetraacetic acid monoamide conjugate of 2-nitroimidazole (GdDO3NI), a magnetic resonance imaging T 1- shortening agent, in hypoxic cells grown in tissue culture. We now report evidence for accumulation of GdDO3NI in hypoxic tumor tissue in vivo. Our data show that GdDO3NI accumulated significantly (p < 0.05) in the central, poorly perfused regions of rat prostate adenocarcinoma AT1 tumors (threefold higher concentration than for the control agent) and showed better clearance from well-perfused regions and complete clearance from the surrounding muscle tissue. Inductively coupled plasma mass spectroscopy confirmed that more GdDO3NI than control agent was retained in the central region and that more GdDO3NI was retained in the central region than at the periphery. These results show the utility of GdDO3NI to image tumor hypoxia and highlight the potential of GdDO3NI for application to image-guided interventions for radiation therapy or hypoxia-activated chemotherapy.

Original languageEnglish (US)
Pages (from-to)271-279
Number of pages9
JournalJournal of Biological Inorganic Chemistry
Volume19
Issue number2
DOIs
StatePublished - Feb 2014

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Nitroimidazoles
Magnetic resonance imaging
Contrast Media
Tumors
Metals
Imaging techniques
Image-Guided Radiotherapy
Radiotherapy
Gadolinium
Prostate
Mass Spectrometry
Neoplasms
Tissue
Adenocarcinoma
Tissue culture
Magnetic Resonance Imaging
Chemotherapy
Neoplasm Metastasis
Inductively coupled plasma
Drug Therapy

Keywords

  • Hypoxia
  • Magnetic resonance imaging
  • Nitroimidazole
  • Prostate tumors

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

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title = "GdDO3NI, a nitroimidazole-based T 1 MRI contrast agent for imaging tumor hypoxia in vivo Topical Issue on Metal-Based MRI Contrast Agents. Guest editor: Valerie C. Pierre",
abstract = "Tumor hypoxia is known to affect sensitivity to radiotherapy and promote development of metastases; therefore, the ability to image tumor hypoxia in vivo could provide useful prognostic information and help tailor therapy. We previously demonstrated in vitro evidence for selective accumulation of a gadolinium tetraazacyclododecanetetraacetic acid monoamide conjugate of 2-nitroimidazole (GdDO3NI), a magnetic resonance imaging T 1- shortening agent, in hypoxic cells grown in tissue culture. We now report evidence for accumulation of GdDO3NI in hypoxic tumor tissue in vivo. Our data show that GdDO3NI accumulated significantly (p < 0.05) in the central, poorly perfused regions of rat prostate adenocarcinoma AT1 tumors (threefold higher concentration than for the control agent) and showed better clearance from well-perfused regions and complete clearance from the surrounding muscle tissue. Inductively coupled plasma mass spectroscopy confirmed that more GdDO3NI than control agent was retained in the central region and that more GdDO3NI was retained in the central region than at the periphery. These results show the utility of GdDO3NI to image tumor hypoxia and highlight the potential of GdDO3NI for application to image-guided interventions for radiation therapy or hypoxia-activated chemotherapy.",
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AU - Sherry, A. Dean

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AB - Tumor hypoxia is known to affect sensitivity to radiotherapy and promote development of metastases; therefore, the ability to image tumor hypoxia in vivo could provide useful prognostic information and help tailor therapy. We previously demonstrated in vitro evidence for selective accumulation of a gadolinium tetraazacyclododecanetetraacetic acid monoamide conjugate of 2-nitroimidazole (GdDO3NI), a magnetic resonance imaging T 1- shortening agent, in hypoxic cells grown in tissue culture. We now report evidence for accumulation of GdDO3NI in hypoxic tumor tissue in vivo. Our data show that GdDO3NI accumulated significantly (p < 0.05) in the central, poorly perfused regions of rat prostate adenocarcinoma AT1 tumors (threefold higher concentration than for the control agent) and showed better clearance from well-perfused regions and complete clearance from the surrounding muscle tissue. Inductively coupled plasma mass spectroscopy confirmed that more GdDO3NI than control agent was retained in the central region and that more GdDO3NI was retained in the central region than at the periphery. These results show the utility of GdDO3NI to image tumor hypoxia and highlight the potential of GdDO3NI for application to image-guided interventions for radiation therapy or hypoxia-activated chemotherapy.

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