title: GdDO3NI, a nitroimidazole-based T1 MRI contrast agent for imaging tumor hypoxia in vivo.
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.
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Gulaka
authors.forename: Federico
authors.initials: F
authors.lastname: Rojas-Quijano
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Kovacs
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Mason
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
authors.forename: Vikram D
authors.initials: VD
authors.lastname: Kodibagkar
mesh_terms: D000818:Animals; D001692:Biological Transport; D015687:Cell Hypoxia; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009593:Nitroimidazoles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology*; D051381:Rats
chemical_list: D003287:Contrast Media; D009593:Nitroimidazoles; D009942:Organometallic Compounds; D005682:Gadolinium