Endogenous Chemical Exchange Saturation Transfer MRI for the Diagnosis and Therapy Response Assessment of Brain Tumors: A Systematic Review

Okuchi, Sachi; Hammam, Ahmed; Golay, Xavier; Kim, Mina; Thust, Stefanie

doi:10.1148/rycan.2020190036

Cited by 11 publications

(18 citation statements)

References 49 publications

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“…MTR asym (3.5 ppm) is the most widely used metric for APT, which has demonstrated correlations with histological grade in brain tumors and could differentiate tumor recurrence from radiation necrosis [ 6 , 8 , 28 ]. However, MTR asym (3.5 ppm) includes multiple saturation-transfer effects from amide protons (3.5 ppm), aliphatic protons (−3.5 ppm), and semisolid macromolecules and is, therefore, termed an APT-weighted (APTw) image.…”

Section: Principle Of Cestmentioning

confidence: 99%

“…Particularly, CEST imaging has been explored in assessing tumor metabolism, pH microenvironment, and histological types [ 4 , 5 , 6 ]. Like other MR techniques, CEST has been intensively investigated for characterizing brain tumors, with several dedicated reviews [ 6 , 8 ]. CEST has also been widely studied in non-brain tumors, especially in recent years with the progress in CEST acquisition sequences and post-processing methods.…”

Section: Introductionmentioning

confidence: 99%

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A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

Gao

Zou

et al. 2021

IJMS

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Chemical exchange saturation transfer (CEST) MRI is a promising molecular imaging tool which allows the specific detection of metabolites that contain exchangeable amide, amine, and hydroxyl protons. Decades of development have progressed CEST imaging from an initial concept to a clinical imaging tool that is used to assess tumor metabolism. The first translation efforts involved brain imaging, but this has now progressed to imaging other body tissues. In this review, we summarize studies using CEST MRI to image a range of tumor types, including breast cancer, pelvic tumors, digestive tumors, and lung cancer. Approximately two thirds of the published studies involved breast or pelvic tumors which are sites that are less affected by body motion. Most studies conclude that CEST shows good potential for the differentiation of malignant from benign lesions with a number of reports now extending to compare different histological classifications along with the effects of anti-cancer treatments. Despite CEST being a unique ‘label-free’ approach with a higher sensitivity than MR spectroscopy, there are still some obstacles for implementing its clinical use. Future research is now focused on overcoming these challenges. Vigorous ongoing development and further clinical trials are expected to see CEST technology become more widely implemented as a mainstream imaging technology.

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Section: Principle Of Cestmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

Gao

Zou

et al. 2021

IJMS

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“…Molecular MRI techniques-such as MR spectroscopy and chemical exchange saturation transfer (CEST)-could improve tumor specificity of MRI by visualizing molecules that are specific to tumor metabolism, but these have not yet been fully integrated into standard clinical care [2,3]. Positron emission tomography (PET) is similar to metabolic MRI in that it targets molecular characteristics of human tissues.…”

Section: Introductionmentioning

confidence: 99%

CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [68Ga]Ga-Pentixafor /[177Lu]Lu-Pentixather

Jacobs

Wesseling

Keizer

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose CXCR4 (over)expression is found in multiple human cancer types, while expression is low or absent in healthy tissue. In glioblastoma it is associated with a poor prognosis and more extensive infiltrative phenotype. CXCR4 can be targeted by the diagnostic PET agent [68Ga]Ga-Pentixafor and its therapeutic counterpart [177Lu]Lu-Pentixather. We aimed to investigate the expression of CXCR4 in glioblastoma tissue to further examine the potential of these PET agents. Methods CXCR4 mRNA expression was examined using the R2 genomics platform. Glioblastoma tissue cores were stained for CXCR4. CXCR4 staining in tumor cells was scored. Stained tissue components (cytoplasm and/or nuclei of the tumor cells and blood vessels) were documented. Clinical characteristics and information on IDH and MGMT promoter methylation status were collected. Seven pilot patients with recurrent glioblastoma underwent [68Ga]Ga-Pentixafor PET; residual resected tissue was stained for CXCR4. Results Two large mRNA datasets (N = 284; N = 540) were assesed. Of the 191 glioblastomas, 426 cores were analyzed using immunohistochemistry. Seventy-eight cores (23 tumors) were CXCR4 negative, while 18 cores (5 tumors) had both strong and extensive staining. The remaining 330 cores (163 tumors) showed a large inter- and intra-tumor variation for CXCR4 expression; also seen in the resected tissue of the seven pilot patients—not directly translatable to [68Ga]Ga-Pentixafor PET results. Both mRNA and immunohistochemical analysis showed CXCR4 negative normal brain tissue and no significant correlation between CXCR4 expression and IDH or MGMT status or survival. Conclusion Using immunohistochemistry, high CXCR4 expression was found in a subset of glioblastomas as well as a large inter- and intra-tumor variation. Caution should be exercised in directly translating ex vivo CXCR4 expression to PET agent uptake. However, when high CXCR4 expression can be identified with [68Ga]Ga-Pentixafor, these patients might be good candidates for targeted radionuclide therapy with [177Lu]Lu-Pentixather in the future.

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“… 45 Okuchi and colleagues conducted a systematic review on the use of endogenous CEST for the diagnosis and therapy response assessment of brain tumours. 46 They found four studies that sought to assess the potential of CEST to differentiate tumour recurrence from treatment related changes, including a total of 161 glioma patients imaged on 3 T MRI systems. 47–50 All studies used APT imaging.…”

Section: Introductionmentioning

confidence: 99%

“…Two further studies have investigated the potential of CEST in assessing gliomas’ response and predicting their prognosis. 46,51,52 Regnery et al reported that pre-treatment tumour signal in Nuclear Overhauser Enhancement - Lorentzian difference differed significantly based on responsiveness to first-line treatment, with an AUC of 0.98. 51 Harris et al showed that tumours that were acidic at baseline, as defined by a > 50% region of positive CEST asymmetry at 3.0 ppm, had a significantly longer progression free survival (PFS) compared to patients whose tumours weren't acidic (log-rank, p < .0001; median PFS for acidic tumours vs non-acidic tumours = 125 days vs 450 days).…”

Section: Introductionmentioning

confidence: 99%

Glioma surveillance imaging: current strategies, shortcomings, challenges and outlook

et al. 2020

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Inaccurate assessment of surveillance imaging to assess response to glioma therapy may have life-changing consequences. Varied management plans including chemotherapy, radiotherapy or immunotherapy may all contribute to heterogeneous post-treatment appearances and the overlap between the morphological features of pseudoprogression, pseudoresponse and radiation necrosis can make their discrimination very challenging. Therefore, there has been a drive to develop objective strategies for post-treatment assessment of brain gliomas. This review discusses the most important of these approaches such as the RANO “Response Assessment in Neuro-Oncology”, iRANO “Immunotherapy Response Assessment in Neuro-Oncology” and RAPNO “Response Assessment in Paediatric Neuro-Oncology” models. In addition to these systematic approaches for glioma surveillance, the relatively limited information provided by conventional imaging modalities alone has motivated the development of novel advanced magnetic resonance (MR) and metabolic imaging methods for further discrimination between viable tumour and treatment induced changes. Multiple clinical trials and meta-analyses have investigated the diagnostic performance of these novel techniques in the follow up of brain gliomas, including both single modality descriptive studies and comparative imaging assessment. In this manuscript, we review the literature and discuss the promises and pitfalls of frequently studied modalities in glioma surveillance imaging, including MR perfusion, MR diffusion and MR spectroscopy. In addition, we evaluate other promising MR techniques such as chemical exchange saturation transfer as well as fludeoxyglucose and non-FDG positron emission tomography techniques.

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Endogenous Chemical Exchange Saturation Transfer MRI for the Diagnosis and Therapy Response Assessment of Brain Tumors: A Systematic Review

Cited by 11 publications

References 49 publications

A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

A Brief History and Future Prospects of CEST MRI in Clinical Non-Brain Tumor Imaging

CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [68Ga]Ga-Pentixafor /[177Lu]Lu-Pentixather

Glioma surveillance imaging: current strategies, shortcomings, challenges and outlook

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