A Comparative Study of the Hypoxia PET Tracers [18F]HX4, [18F]FAZA, and [18F]FMISO in a Preclinical Tumor Model

Peeters, Sarah G.J.A.; Zegers, Catharina M.L.; Lieuwes, Natasja G.; Elmpt, Wouter van; Eriksson, Jonas; Dongen, Guus A.M.S. van; Dubois, Ludwig; Lambin, Philippe

doi:10.1016/j.ijrobp.2014.09.045

Cited by 138 publications

(110 citation statements)

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“…However, these results were obtained at 80–90 min post injection, a time point which is probably too early for evaluation since normal tissue clearance is still ongoing. Cu-ATSM had the highest tumour accumulation and low renal clearance compared to fluorinated nitroimidazoles Peeters et al [211]In a comparative study within a rat rhabdomyosarcoma model, FMISO, FAZA, and HX4 uptake (tumour to blood ratio (TBR)), reproducibility and reversibility were assessed. Blood clearance for FAZA and HX4 was similar 3 h p.i., while for FMISO, as expected, clearance from normal tissues was significantly lower.…”

Section: Methodsmentioning

confidence: 99%

Molecular mechanisms of hypoxia in cancer

Challapalli¹,

Carroll

Aboagye

2017

Clin Transl Imaging

123

108

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PurposeHypoxia is a condition of insufficient oxygen to support metabolism which occurs when the vascular supply is interrupted, or when a tumour outgrows its vascular supply. It is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. This review provides an overview of hypoxia imaging with Positron emission tomography (PET), with an emphasis on the biological relevance, mechanism of action, highlighting advantages, and limitations of the currently available hypoxia radiotracers.MethodsA comprehensive PubMed literature search was performed, identifying articles relating to biological significance and measurement of hypoxia, MRI methods, and PET imaging of hypoxia in preclinical and clinical settings, up to December 2016.ResultsA variety of approaches have been explored over the years for detecting and monitoring changes in tumour hypoxia, including regional measurements with oxygen electrodes placed under CT guidance, MRI methods that measure either oxygenation or lactate production consequent to hypoxia, different nuclear medicine approaches that utilise imaging agents the accumulation of which is inversely related to oxygen tension, and optical methods. The advantages and disadvantages of these approaches are reviewed, along with individual strategies for validating different imaging methods. PET is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels.ConclusionEven though hypoxia could have significant prognostic and predictive value in the clinic, the best method for hypoxia assessment has in our opinion not been realised.

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Section: Methodsmentioning

confidence: 99%

Molecular mechanisms of hypoxia in cancer

Challapalli¹,

Carroll

Aboagye

2017

Clin Transl Imaging

123

108

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“…In a second comparative study, 18 F-HX4 and 18 F-FAZA were found to be sensitive to an increase of hypoxia, induced by the breathing of a gas mixture containing 7% O 2 , when the tumor-to-blood ratio was used. However, when only the tumor-to-muscle was used, only 18 F-FAZA revealed a significant decrease in tumor oxygenation (41). …”

Section: Positron Emission Tomographymentioning

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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“…The call for more individualized approach to cancer treatment challenges future studies to investigate prospectively whether risk stratification of patients by means of metabolic parameters will lead to change of management and significant improvement in patients’ survival. Moreover, it should be recognized that the benefit of PET imaging can be extended by using different tracers for different biological features such as hypoxia level, which in turn is associated with negative effect on prognosis [37–39]. Perhaps this can lead to promising risk stratification tools that combine different biological imaging markers based on an entirely non-invasive method.…”

Section: Discussionmentioning

confidence: 99%

18F-FDG PET as novel imaging biomarker for disease progression after ablation therapy in colorectal liver metastases

Samim

Prevoo

Veen

et al. 2017

Eur J Nucl Med Mol Imaging

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PurposeRecurrent disease following thermal ablation therapy is a frequently reported problem. Preoperative identification of patients with high risk of recurrent disease might enable individualized treatment based on patients’ risk profile. The aim of the present work was to investigate the role of metabolic parameters derived from the pre-ablation 18F-FDG PET/CT as imaging biomarkers for recurrent disease in patients with colorectal liver metastases (CLM).MethodsIncluded in this retrospective study were all consecutive patients with CLM treated with percutaneous or open thermal ablation therapy who had a pre-treatment baseline 18F-FDG PET/CT available. Multivariable cox regression for survival analysis was performed using different models for the metabolic parameters (SULpeak, SULmean, SULmax, partial volume corrected SULmean (cSULmean), and total lesion glycolysis (TLG)) corrected for tumour and procedure characteristics. The study endpoints were defined as local tumour progression free survival (LTP-FS), new intrahepatic recurrence free survival (NHR-FS) and extrahepatic recurrence free survival (EHR-FS). Clinical and imaging follow-up data was used as the reference standard.ResultsFifty-four patients with 90 lesions were selected. Univariable cox regression analysis resulted in eight models. Multivariable analysis revealed that after adjusting for lesion size and the approach of the procedure, none of the metabolic parameters were associated with LTP-FS or EHR-FS. Percutaneous approach was significantly associated with a shorter LTP-FS. It was demonstrated that lower values of SULpeak, SULmax, SULmean , and cSULmean are associated with a significant better NHR-FS, independent of the lesion size and number and prior chemotherapy.ConclusionWe found no association between the metabolic parameters on pre-ablation 18F-FDG PET/CT and the LTP-FS. However, low values of the metabolic parameters were significantly associated with improved NHR-FS. The clinical implication of these findings might be the identification of high-risk patients who might benefit most from adjuvant or combined treatment strategies.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-017-3637-0) contains supplementary material, which is available to authorized users.

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A Comparative Study of the Hypoxia PET Tracers [18F]HX4, [18F]FAZA, and [18F]FMISO in a Preclinical Tumor Model

Abstract: This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be put forward.

Cited by 138 publications

References 30 publications

Molecular mechanisms of hypoxia in cancer

Molecular mechanisms of hypoxia in cancer

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

18F-FDG PET as novel imaging biomarker for disease progression after ablation therapy in colorectal liver metastases

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