MRI assessment of changes in tumor oxygenation post hypoxia-targeted therapy

Agarwal, Shalabh; Shankar, Rohini Vidya; Inge, Landon J.; Kodibagkar, Vikram D.

doi:10.1117/12.2083926

Cited by 5 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oxygen tensions can be determined from changes in relaxivity of perfluorcarbons ( 19 F MRSI) or HMDSO ( 1 H MRSI) obtained using spectroscopic MRI of the tumor following intratumoral injections [65,66]. These approaches have been used to understand the role of hypoxia in resistance to radiation therapy in preclinical models [67] but have not been attempted in human studies.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Molecular and functional imaging insights into the role of hypoxia in cancer aggression

Kakkad

Krishnamachary

Jacob

et al. 2019

Cancer Metastasis Rev

View full text Add to dashboard Cite

Hypoxia in cancers has evoked significant interest since 1955 when Thomlinson and Gray postulated the presence of hypoxia in human lung cancers, based on the observation of necrosis occurring at the diffusion limit of oxygen from the nearest blood vessel, and identified the implication of these observations for radiation therapy. Coupled with discoveries in 1953 by Gray and others that anoxic cells were resistant to radiation damage, these observations have led to an entire field of research focused on exploiting oxygenation and hypoxia to improve the outcome of radiation therapy. Almost 65 years later, tumor heterogeneity of nearly every parameter measured including tumor oxygenation, and the dynamic landscape of cancers and their microenvironments are clearly evident, providing a strong rationale for cancer personalized medicine. Since hypoxia is a major cause of extracellular acidosis in tumors, here we have focused on the applications of imaging to understand the effects of hypoxia in tumors and to target hypoxia in theranostic strategies.

show abstract

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Molecular and functional imaging insights into the role of hypoxia in cancer aggression

Kakkad

Krishnamachary

Jacob

et al. 2019

Cancer Metastasis Rev

View full text Add to dashboard Cite

show abstract

“…BOLD and tissue oxygen level-dependent (TOLD) signal (34)(35)(36)(37) nitroimidazole (GdDO3NI, MW = 839 g/mol), was used to measure hypoxia, noninvasively by MRI, in vitro using 9L glioma cells (44) and in vivo in a rat prostate cancer model (45) and MRI contrast enhancement showed correlation with pimonidazole staining. The relaxivity values of GdDO3NI were reported as r1=4.75±0.04 s -1 mM -1 and r2 =7.52±0.07 s -1 mM -1 at 37 °C and 7 T (46).…”

Section: Introductionmentioning

confidence: 99%

GdDO3NI allows imaging of hypoxia after brain injury

Moghadas

Bharadwaj

Tobey

et al. 2021

Preprint

View full text Add to dashboard Cite

Purpose: In this study, we use the hypoxia targeting agent (GdDO3NI, a nitroimidazole-based T1 MRI contrast agent) for imaging hypoxia in the injured brain after experimental traumatic brain injury (TBI) using magnetic resonance imaging (MRI), and validate the results with immunohistochemistry (IHC) using pimonidazole. Methods: TBI induced mice (controlled cortical impact model) were imaged at 7T using a T2 weighted fast spin-echo sequence to estimate the extent of the injury. The mice were then were intravenously injected with either conventional T1 agent (gadoteridol) or GdDO3NI at 0.3 mmol/kg dose (n=5 for each cohort) along with pimonidazole (60 mg/kg). Mice were imaged pre- and post-contrast using a T1-weighted spin-echo sequence for three hours. Regions of interests were drawn on the brain injury region, the contralateral brain as well as on the cheek muscle region for comparison of contrast kinetics. Brains were harvested immediately post imaging for immunohistochemical analysis. Results: GdDO3NI is retained in the injury region for up to 3 hours post-injection (p< 0.05 compared to gadoteridol) while it rapidly clears out of the muscle region. On the other hand, conventional MRI contrast agent gadoteridol clears out of both the injury region and muscle rapidly, although with a relatively more delayed wash out in the injury region. Minimal contrast enhancement was seen for both agents in the contralateral hemisphere. Pimonidazole staining confirms the presence of hypoxia in both gadoteridol and GdDO3NI cohorts, and the later cohort shows good agreement with MRI contrast enhancement. Conclusion: GdDO3NI was successfully shown to visualize hypoxia in the brain post-TBI using T1-wt MRI.

show abstract

“…This indicated that the targeting observed with GdDO3NI was attributable only to hypoxia and not due to differences in molecular weight or the hydrophobicity of the linker arm. More recently, the relaxivity values of GdDO3NI were reported as r 1 = 4.75 AE 0.04 s/ mM and r 2 = 7.52 AE 0.07 s/mM at 37 C and 7 T. 23 The objectives of the present study were 1) to utilize GdDO3NI enhanced MRI, for high-resolution visualization of hypoxia in the rodent brain post TBI; 2) to validate MRI data with pimonidazole-based IHC; and 3) to assess any nonspecific retention of gadoteridol (a clinically approved macrocyclic agent) in TBI that may arise due to an evolving BBB.…”

mentioning

confidence: 99%

GdDO3NI Enhanced Magnetic Resonance Imaging Allows Imaging of Hypoxia After Brain Injury

Moghadas

Bharadwaj

Tobey

et al. 2021

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Background: Brain tissue hypoxia is a common consequence of traumatic brain injury (TBI) due to the rupture of blood vessels during impact and it correlates with poor outcome. The current magnetic resonance imaging (MRI) techniques are unable to provide a direct map of tissue hypoxia. Purpose: To investigate whether GdDO3NI, a nitroimidazole-based T 1 MRI contrast agent allows imaging hypoxia in the injured brain after experimental TBI. Study Type: Prospective. Animal Model: TBI-induced mice (controlled cortical impact model) were intravenously injected with either conventional T 1 agent (gadoteridol) or GdDO3NI at 0.3 mmol/kg dose (n = 5 for each cohort) along with pimonidazole (60 mg/kg) at 1 hour postinjury and imaged for 3 hours following which they were euthanized. Field Strength/Sequence: 7 T/T 2 -weighted spin echo and T 1 -weighted gradient echo. Assessment: Injured animals were imaged with T 2 -weighted spin-echo sequence to estimate the extent of the injury. The mice were then imaged precontrast and postcontrast using a T 1 -weighted gradient-echo sequence for 3 hours postcontrast. Regions of interests were drawn on the brain injury region, the contralateral brain as well as on the cheek muscle region for comparison of contrast kinetics. Brains were harvested immediately post-imaging for immunohistochemical analysis. Statistical Tests: One-way analysis of variance and two-sample t-tests were performed with a P < 0.05 was considered statistically significant. Results: GdDO3NI retention in the injury region at 2.5-3 hours post-injection was significantly higher compared to gadoteridol (mean retention fraction 63.95% AE 27.43% vs. 20.68% AE 7.43% for gadoteridol at 3 hours) while it rapidly cleared out of the muscle region. Pimonidazole staining confirmed the presence of hypoxia in both gadoteridol and GdDO3NI cohorts, and the later cohort showed good agreement with MRI contrast enhancement. Data Conclusion: GdDO3NI was successfully shown to visualize hypoxia in the brain post-TBI using T 1 -weighted MRI at 2.5-3 hours postcontrast.

show abstract

MRI assessment of changes in tumor oxygenation post hypoxia-targeted therapy

Cited by 5 publications

References 21 publications

Molecular and functional imaging insights into the role of hypoxia in cancer aggression

Molecular and functional imaging insights into the role of hypoxia in cancer aggression

GdDO3NI allows imaging of hypoxia after brain injury

GdDO3NI Enhanced Magnetic Resonance Imaging Allows Imaging of Hypoxia After Brain Injury

Contact Info

Product

Resources

About