Hypoxia Imaging As a Guide for Hypoxia-Modulated and Hypoxia-Activated Therapy

Brender, Jeffrey R.; Saida, Yu; Devasahayam, Nallathamby; Cherukuri, Murali Krishna; Kishimoto, Shun

doi:10.1089/ars.2021.0176

Cited by 16 publications

(17 citation statements)

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“…However, histological assessment for oxygenation is not quantitative and is not a fully reliable method for the detection of hypoxia because it depends both on pimonidazole perfusion and local redox status. [47] In the current study, we employed EPR imaging for the non-invasive and quantitative assessment of pO 2 following PEGPH20 treatment. The results showed that pO 2 significantly increased by 4.8 mmHg after treatment with PEGPH20 in BxPC3-HAS3 tumors, while pO 2 significantly decreased by 2.1 mmHg in tumors treated by the vehicle ( Figure 2 D).…”

Section: Discussionmentioning

confidence: 99%

PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

et al. 2022

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Section: Discussionmentioning

confidence: 99%

PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

et al. 2022

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“…Recent technological advances have facilitated deeper understanding of the complex changes in carbohydrate, amino acid, and lipid metabolism and thereby provide opportunities for targeted molecular imaging and therapeutic interventions. Several functional imaging modalities to detect pathophysiological information of tumor are recently developed to aid cancer research [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. An appropriate therapeutic treatment can be planned based on the prior information derived from functional imaging.…”

Section: Introductionmentioning

confidence: 99%

EPR and Related Magnetic Resonance Imaging Techniques in Cancer Research

et al. 2023

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Imaging tumor microenvironments such as hypoxia, oxygenation, redox status, and/or glycolytic metabolism in tissues/cells is useful for diagnostic and prognostic purposes. New imaging modalities are under development for imaging various aspects of tumor microenvironments. Electron Paramagnetic Resonance Imaging (EPRI) though similar to NMR/MRI is unique in its ability to provide quantitative images of pO2 in vivo. The short electron spin relaxation times have been posing formidable challenge to the technology development for clinical application. With the availability of the narrow line width trityl compounds, pulsed EPR imaging techniques were developed for pO2 imaging. EPRI visualizes the exogenously administered spin probes/contrast agents and hence lacks the complementary morphological information. Dynamic nuclear polarization (DNP), a phenomenon that transfers the high electron spin polarization to the surrounding nuclear spins (1H and 13C) opened new capabilities in molecular imaging. DNP of 13C nuclei is utilized in metabolic imaging of 13C-labeled compounds by imaging specific enzyme kinetics. In this article, imaging strategies mapping physiologic and metabolic aspects in vivo are reviewed within the framework of their application in cancer research, highlighting the potential and challenges of each of them.

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“…These factors have led to the development of various techniques for determining the oxygenation status of tumors. [7][8][9][10] EPR-based techniques offer high sensitivity to measure the partial pressure of oxygen (pO 2 ) of hypoxic tumors because of the inverse relationship between the oxygen level and EPR signal intensity. With the advantage of versatile and well-studied nitroxyl spin probes and relatively simple instrumentation, the continuous wave (CW) EPR techniques have been on the forefront in the development and application of EPR based oximetry.…”

Section: Introductionmentioning

confidence: 99%

“…Hypoxia plays a crucial role in the progression and metastasis of many cancers and is strongly correlated with poor prognosis. The success of some therapeutic treatments, such as radiotherapy 1,2 and some types of chemotherapy, 2–6 can also hinge on the oxygen levels within the tumor. These factors have led to the development of various techniques for determining the oxygenation status of tumors 7–10 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a deuterated triarylmethyl spin probe for in vivo R₂∗‐based EPR oximetric imaging with enhanced dynamic range

Kishimoto,

Devasahayam,

Chandramouli

et al. 2023

Magnetic Resonance in Med

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PurposeIn this study, we compared two triarylmethyl (TAM) spin probes, Ox071 and Ox063 for their efficacy in measuring tissue oxygen levels under hypoxic and normoxic conditions by R2*‐based EPR oximetry.MethodsThe R2* dependencies on the spin probe concentration and oxygen level were calibrated using deoxygenated 1, 2, 5, and 10 mM standard solutions and 2 mM solutions saturated at 0%, 2%, 5%, 10%, and 21% of oxygen. For the hypoxic model, in vivo imaging of a MIA PaCa‐2 tumor implanted in the hind leg of a mouse was performed on successive days by R2*‐based EPR oximetry using either Ox071 or Ox063. For the normoxic model, renal imaging of healthy athymic mice was performed using both spin probes. The 3D images were reconstructed by single point imaging and multi‐gradient technique was used to determine R2* maps.ResultsThe signal intensities of Ox071 were approximately three times greater than that of Ox063 in the entire partial pressure of oxygen (pO2) range investigated. The histograms of the tumor pO2 images were skewed for both spin probes, and Ox071 showed more frequency counts at pO2 > 32 mm Hg. In the normoxic kidney model, there was a clear delineation between the high pO2 cortex and the low pO2 medulla regions. The histogram of high‐resolution kidney oximetry image using Ox071 was nearly symmetrical and frequency counts were seen up to 55 mm Hg, which were missed in Ox063 imaging.ConclusionAs an oximetric probe, Ox071 has clear advantages over Ox063 in terms of sensitivity and the pO2 dynamic range.

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Hypoxia Imaging As a Guide for Hypoxia-Modulated and Hypoxia-Activated Therapy

Cited by 16 publications

References 145 publications

PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

EPR and Related Magnetic Resonance Imaging Techniques in Cancer Research

Evaluation of a deuterated triarylmethyl spin probe for in vivo R₂∗‐based EPR oximetric imaging with enhanced dynamic range

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Hypoxia Imaging As a Guide for Hypoxia-Modulated and Hypoxia-Activated Therapy

Cited by 16 publications

References 145 publications

PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

PEGPH20, a PEGylated human hyaluronidase, induces radiosensitization by reoxygenation in pancreatic cancer xenografts. A molecular imaging study

EPR and Related Magnetic Resonance Imaging Techniques in Cancer Research

Evaluation of a deuterated triarylmethyl spin probe for in vivo R2∗‐based EPR oximetric imaging with enhanced dynamic range

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Evaluation of a deuterated triarylmethyl spin probe for in vivo R₂∗‐based EPR oximetric imaging with enhanced dynamic range