Monitoring Tumor Response to Carbogen Breathing by Oxygen-Sensitive Magnetic Resonance Parameters to Predict the Outcome of Radiation Therapy: A Preclinical Study

Cao-Pham, Thanh-Trang; Tran, Ly-Binh-An; Colliez, Florence; Joudiou, Nicolas; Bachiri, Sabrina El; Grégoire, Vincent; Lévêque, Philippe; Gallez, Bernard; Jordan, Bénédicte F.

doi:10.1016/j.ijrobp.2016.04.029

Cited by 23 publications

(16 citation statements)

References 28 publications

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“…Lipid also exhibits relatively lower signal to noise ratio. Oddly, a follow up study examining relative R 1 responses in 9L-glioma and rhabdomyosarcoma found smaller response for lipid R 1 than water R 1 [47]. This recent work indicated that only R 2 * had predictive value with respect to tumor irradiation and this applied to subcutaneous 9L glioma in rat, but not rhabdomyosarcoma.…”

Section: Discussionmentioning

confidence: 98%

Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging

et al. 2017

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Radiation therapy is a primary treatment for non-resectable lung cancer and hypoxia is thought to influence tumor response. Hypoxia is expected to be particularly relevant to the evolving new radiation treatment scheme of hypofractionated stereotactic body radiation therapy (SBRT). As such, we sought to develop non-invasive tools to assess tumor pathophysiology and response to irradiation. We applied blood oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) MRI, together with dynamic contrast enhanced (DCE) MRI to explore the longitudinal effects of SBRT on tumor oxygenation and vascular perfusion using A549 human lung cancer xenografts in a subcutaneous rat model. Intra-tumor heterogeneity was seen on multi-parametric maps, especially in BOLD, T2* and DCE. At baseline, most tumors showed a positive BOLD signal response (%ΔSI) and increased T2* in response to oxygen breathing challenge, indicating increased vascular oxygenation. Control tumors showed similar response 24 hours and 1 week later. Twenty-four hours after a single dose of 12 Gy, the irradiated tumors showed a significantly decreased T2* (-2.9±4.2 ms) and further decrease was observed (-4.0±6.0 ms) after 1 week, suggesting impaired vascular oxygenation. DCE revealed tumor heterogeneity, but showed minimal changes following irradiation. Rats were cured of the primary tumors by 3×12 Gy, providing long term survival, though with ultimate metastatic recurrence.

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Section: Discussionmentioning

confidence: 98%

Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging

et al. 2017

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“…Multiple mechanisms may play a determining role at an early stage, and then the others may become predominant at a later stage. In this case, the non‐invasive magnetic resonance imaging (MRI) based methods, such as R2*‐MRI to detect deoxyhaemoglobin content and Dynamic Contrast‐Enhanced MRI to characterize vascular network, would be helpful to further explore the mode of action of ITPP over the course of treatment.…”

Section: Discussionmentioning

confidence: 99%

Impact of myo‐inositol trispyrophosphate (ITPP) on tumour oxygenation and response to irradiation in rodent tumour models

Tran

Cao-Pham

Jordan

et al. 2018

J Cellular Molecular Medi

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Tumour hypoxia is a well‐established factor of resistance in radiation therapy (RT). Myo ‐inositol trispyrophosphate (ITPP) is an allosteric effector that reduces the oxygen‐binding affinity of haemoglobin and facilitates the release of oxygen by red blood cells. We investigated herein the oxygenation effect of ITPP in six tumour models and its radiosensitizing effect in two of these models. The evolution of tumour pO 2 upon ITPP administration was monitored on six models using 1.2 GHz Electron Paramagnetic Resonance (EPR) oximetry. The effect of ITPP on tumour perfusion was assessed by Hoechst staining and the oxygen consumption rate (OCR) in vitro was measured using 9.5 GHz EPR. The therapeutic effect of ITPP with and without RT was evaluated on rhabdomyosarcoma and 9L‐glioma rat models. ITPP enhanced tumour oxygenation in six models. The administration of 2 g/kg ITPP once daily for 2 days led to a tumour reoxygenation for at least 4 days. ITPP reduced the OCR in six cell lines but had no effect on tumour perfusion when tested on 9L‐gliomas. ITPP plus RT did not improve the outcome in rhabdomyosarcomas. In 9L‐gliomas, some of tumours receiving the combined treatment were cured while other tumours did not benefit from the treatment. ITPP increased oxygenation in six tumour models. A decrease in OCR could contribute to the decrease in tumour hypoxia. The association of RT with ITPP was beneficial for a few 9L‐gliomas but was absent in the rhabdomyosarcomas.

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“…An alternative method based on the deconvolution of global T 1 in fat and water components was recently developed. However, a quantitative aspect could not be demonstrated in rhabdomyosarcomas and glioma models, and lipids T 1 and global T 1 turned out to be less predictive of the outcome of radiation therapy than

R_{2}^{*}

(101). Considering the clinical application of MOBILE, the method has demonstrated its ability to identify hypoxia in stroke areas (124).…”

Section: Mri Methodsmentioning

confidence: 96%

“…However, the inhibition of tumor growth exhibited with the RIF-1 fibrosarcoma was smaller, and this was related to a low

R_{2}^{*}

at baseline and to a poor response to the hyperoxic challenge (100). Recently, our group observed that

R_{2}^{*}

was predictive of radiation therapy outcome in rat 9L-glioma tumors but not in rhabdomyosarcoma tumors (101). In a study by Kim and colleagues, the results from a small sample of cancer cervical patients suggested that the

R_{2}^{*}

values are predictive of the radiotherapeutic response (102).…”

Section: Mri Methodsmentioning

confidence: 99%

Assessing Tumor Oxygenation for Predicting Outcome in Radiation Oncology: A Review of Studies Correlating Tumor Hypoxic Status and Outcome in the Preclinical and Clinical Settings

2017

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Tumor hypoxia is recognized as a limiting factor for the efficacy of radiotherapy, because it enhances tumor radioresistance. It is strongly suggested that assessing tumor oxygenation could help to predict the outcome of cancer patients undergoing radiation therapy. Strategies have also been developed to alleviate tumor hypoxia in order to radiosensitize tumors. In addition, oxygen mapping is critically needed for intensity modulated radiation therapy (IMRT), in which the most hypoxic regions require higher radiation doses and the most oxygenated regions require lower radiation doses. However, the assessment of tumor oxygenation is not yet included in day-to-day clinical practice. This is due to the lack of a method for the quantitative and non-invasive mapping of tumor oxygenation. To fully integrate tumor hypoxia parameters into effective improvements of the individually tailored radiation therapy protocols in cancer patients, methods allowing non-invasively repeated, safe, and robust mapping of changes in tissue oxygenation are required. In this review, non-invasive methods dedicated to assessing tumor oxygenation with the ultimate goal of predicting outcome in radiation oncology are presented, including positron emission tomography used with nitroimidazole tracers, magnetic resonance methods using endogenous contrasts (R1 and R2*-based methods), and electron paramagnetic resonance oximetry; the goal is to highlight results of studies establishing correlations between tumor hypoxic status and patients’ outcome in the preclinical and clinical settings.

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Monitoring Tumor Response to Carbogen Breathing by Oxygen-Sensitive Magnetic Resonance Parameters to Predict the Outcome of Radiation Therapy: A Preclinical Study

Cited by 23 publications

References 28 publications

Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging

Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging

Impact of myo‐inositol trispyrophosphate (ITPP) on tumour oxygenation and response to irradiation in rodent tumour models

Assessing Tumor Oxygenation for Predicting Outcome in Radiation Oncology: A Review of Studies Correlating Tumor Hypoxic Status and Outcome in the Preclinical and Clinical Settings

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