JBIC Journal of Biological Inorganic Chemistry

, Volume 19, Issue 2, pp 271–279

GdDO3NI, a nitroimidazole-based T1 MRI contrast agent for imaging tumor hypoxia in vivo

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

DOI: 10.1007/s00775-013-1058-5

Cite this article as:
Gulaka, P.K., Rojas-Quijano, F., Kovacs, Z. et al. J Biol Inorg Chem (2014) 19: 271. doi:10.1007/s00775-013-1058-5
Part of the following topical collections:
  1. Topical Issue on Metal-Based MRI Contrast Agents

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 T1-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.

Keywords

Magnetic resonance imaging Hypoxia Nitroimidazole Prostate tumors 

Abbreviations

DOTA

Tetraazacyclododecanetetraacetic acid

GdDO3ABA

Gadolinium tetraazacyclododecanetetraacetic acid (n-butyl)monoamide

GdDO3NI

Gadolinium tetraazacyclododecanetetraacetic acid monoamide conjugate of 2-nitroimidazole

GdDTPA

Gadolinium diethylenetriaminepentaacetic acid

GdHPDO3A

Gadolinium 10-(2-hydroxypropyl)-1,4,7-tetraazacyclododecane-1,4,7-triacetic acid

ICP-MS

Inductively coupled plasma mass spectrometry

MR

Magnetic resonance

MRI

Magnetic resonance imaging

PET

Positron emission tomography

Supplementary material

775_2013_1058_MOESM1_ESM.pdf (225 kb)
Supplementary material 1 (PDF 225 kb)

Copyright information

© SBIC 2013

Authors and Affiliations

  • Praveen K. Gulaka
    • 1
    • 4
  • Federico Rojas-Quijano
    • 2
  • Zoltan Kovacs
    • 2
  • Ralph P. Mason
    • 1
  • A. Dean Sherry
    • 1
    • 2
  • Vikram D. Kodibagkar
    • 3
  1. 1.Department of RadiologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Advanced Imaging Research CenterUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.School of Biological and Health Systems EngineeringArizona State UniversityPhoenixUSA
  4. 4.Samsung ElectronicsSuwonSouth Korea

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