FDG—a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer

Zimny, M.; Gagel, Bernd; DiMartino, Ercole; Hamacher, Kurt; Coenen, Heinz H.; Westhofen, Martin; Eble, Michael J.; Buell, U.; Reinartz, Patrick

doi:10.1007/s00259-006-0175-6

Cited by 111 publications

(71 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Preclinical in vivo studies revealed that (96,302), making it a relevant tracer for imaging tumor hypoxia (Fig. 8).…”

Section: The Clinical Importance Of Assessing Tumor Hypoxiamentioning

confidence: 99%

“…However, 18 F-FDG PET imaging, a measure of glucose metabolism, does not distinguish between hypoxic and normoxic tumors when compared against several hypoxia assessment modalities. According to three separate publications, the uptake of 18 F-FDG (SUV max or SUV mean ) in a combined total of 47 H&NC patients was not correlative against common pO 2 descriptors, including HP 2.5 and HP 5 as measured by oxygen-sensitive polarographic electrodes (95,96,302). While there was a reported trend of increasing F-FDG does not appear to be a specific means for assessing tumor hypoxia, its intrinsic value may reside in an ability to help define specific tumor phenotypes that are overtly aggressive, providing mutually complementary information which can be used in conjunction with PET hypoxia data ( Fig.…”

Section: F-ef5 (Pentafluorinated Etanidazole)mentioning

confidence: 99%

See 1 more Smart Citation

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

Walsh

Lebedev

Aten³

et al. 2014

Antioxidants & Redox Signaling

346

317

View full text Add to dashboard Cite

Tumor hypoxia is a well-established biological phenomenon that affects the curability of solid tumors, regardless of treatment modality. Especially for head and neck cancer patients, tumor hypoxia is linked to poor patient outcomes. Given the biological problems associated with tumor hypoxia, the goal for clinicians has been to identify moderately to severely hypoxic tumors for differential treatment strategies. The ''gold standard'' for detecting and characterizing of tumor hypoxia are the invasive polarographic electrodes. Several less invasive hypoxia assessment techniques have also shown promise for hypoxia assessment. The widespread incorporation of hypoxia information in clinical tumor assessment is severely impeded by several factors, including regulatory hurdles and unclear correlation with potential treatment decisions. There is now an acute need for approved diagnostic technologies for determining the hypoxia status of cancer lesions, as it would enable clinical development of personalized, hypoxia-based therapies, which will ultimately improve outcomes. A number of different techniques for assessing tumor hypoxia have evolved to replace polarographic pO 2 measurements for assessing tumor hypoxia. Several of these modalities, either individually or in combination with other imaging techniques, provide functional and physiological information of tumor hypoxia that can significantly improve the course of treatment. The assessment of tumor hypoxia will be valuable to radiation oncologists, surgeons, and biotechnology and pharmaceutical companies who are engaged in developing hypoxia-based therapies or treatment strategies. Antioxid. Redox Signal. 21, 1516-1554.

show abstract

“…Preclinical in vivo studies revealed that (96,302), making it a relevant tracer for imaging tumor hypoxia (Fig. 8).…”

Section: The Clinical Importance Of Assessing Tumor Hypoxiamentioning

confidence: 99%

Section: F-ef5 (Pentafluorinated Etanidazole)mentioning

confidence: 99%

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

Walsh

Lebedev

Aten³

et al. 2014

Antioxidants & Redox Signaling

346

317

View full text Add to dashboard Cite

show abstract

“…In vivo animal model studies have shown that intracellular retention of 18 F-FMISO depends on oxygen concentration, and the rate of 18 F-FMISO binding under hypoxic conditions can be up to 28 times greater than binding under normoxic conditions (13). Many clinical studies have demonstrated an excellent correlation between the 18 F-FMISO uptake and oxygenation status of gliomas, non-small cell lung cancer, head and neck cancer, and cervical cancer (14)(15)(16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

¹⁸F-Fluoromisonidazole PET/CT: A Potential Tool for Predicting Primary Endocrine Therapy Resistance in Breast Cancer

Cheng

et al. 2013

J Nucl Med

View full text Add to dashboard Cite

Although endocrine therapy is an effective method to treat estrogen receptor (ER)-positive breast cancer, approximately 30%-40% of all hormone receptor-positive tumors display de novo resistance. The aim of our current study was to analyze whether 18 F-labeled fluoromisonidazole (1-(2-nitro-1-imidazolyl)-2-hydroxy-3-fluoropropane [ 18 F-FMISO]) PET/CT could predict primary resistance to hormonal therapy in ER-positive breast cancer. Methods: Postmenopausal women who had ER-a-positive breast cancer, stages II-IV, and had never received prior endocrine therapy were prospectively enrolled in this study. Patients underwent both 18 F-FDG and 18 F-FMISO PET/CT scans before and after treatment. The hottest 18 F-FDG standardized uptake value (SUV) in the tumor foci, the SUVs at 2 and 4 h, and the TBR2 h and TBR4 h for the target lesions were calculated (TBR2 h 5 SUV2 h T /SUV2 h B and TBR4 h 5 SUV4 h T /SUV4 h B [TBR is the tumor-to-background ratio]). Clinical outcomes of primary endocrine therapy with letrozole were evaluated according to the criteria of the World Health Organization after at least 3 mo of treatment. Immunohistochemistry for markers of proliferation (Ki67) and hypoxia-induced factor 1a was performed on a subset of tumors that had undergone biopsy or surgery. Pearson and Spearman analysis was used to determine the correlation between the parameters of 18 F-FDG and 18 F-FMISO uptake and clinical or immunohistochemistry outcomes with a 0.01 threshold for statistical significance. Results: A total of 45 lesions (13 primary, 32 metastatic) from 20 patients met the inclusion criteria in this study. Baseline 18 F-FDG and 18 F-FMISO PET/CT scans were obtained for 33 lesions from 16 patients. The correlation between baseline 18 F-FDG uptake and clinical outcome was weak and did not reach statistical significance (r 5 0.37, P 5 0.031). However, there was a significantly positive correlation between baseline 18 F-FMISO uptake (SUV2 h T , TBR2 h, SUV4 h T , and TBR4 h) and clinical outcomes after $3 mo of primary endocrine therapy with letrozole (r 5 0.77, 0.76, 0.71, and 0.78, respectively; P , 0.0001). The application of a TBR4 h cutoff of $1.2 allowed the prediction of 88% of the cases of progressive disease (15/17). Despite poor correlation between 18 F-FMISO uptake and hypoxia-induced factor 1a expression, a marginal positive correlation between TBR4 h and Ki67 expression was measured (r 5 0.51, P 5 0.011) in a subset of malignant lesions acquired by biopsy or surgery. Conclusion: 18 F-FMISO PET/CT can be used to predict primary endocrine resistance in ER-positive breast cancer.

show abstract

“…Dearling et al (45) reported increased 18 F-FDG uptake in the hypoxic regions of human tumour xenografts, when compared with that in normoxic regions and Pugachev et al (46) reported a positive correlation between 18 F-FDG uptake and hypoxia assessed by pimonidazole in nude mice bearing prostate tumours. Conversely, Rajendran et al (47) and Zimny et al (41) showed that hypoxia and glucose uptake are not systematically positively correlated, depending on the histological tumour type, and consecutively on the intrinsic intratumoural microenvironmental conditions affecting diversely glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Measurement of hypoxia using invasive oxygen-sensitive electrode, pimonidazole binding and 18F-FDG uptake in anaemic or erythropoietin-treated mice bearing human glioma xenografts

Scigliano¹,

Pinel²,

Poussier³

et al. 2008

Int J Oncol

View full text Add to dashboard Cite

Abstract.Relationship between haemoglobin levels and tumour oxygenation has been already reported. The purpose of this work was to compare in human malignant gliomabearing mice the sensitivity of two well established techniques of tumour hypoxia assessment, especially their ability to detect expected weak variations of tumour oxygenation status associated to haemoglobin level modifications. The relationship between tumour hypoxia and glucose metabolism was also investigated. Experiments were performed on a human malignant glioma (GBM Nan1) xenografted into nude mice. Twenty-four hours after tumour implantation, animals were randomized into three groups: 'Anaemia' for mice subjected to repeated blood samplings, 'Control', and 'rHuEPO' for mice receiving recombinant human erythropoietin. Once the tumours reached a volume of 300±100 mm 3 , tumour hypoxia was assessed both using the pO 2 -Histograph, Eppendorf™ and the pimonidazole binding assay. Glucose metabolism was evaluated by 18 F-FDG autoradiography and compared with the pimonidazole binding distribution pattern. Repeated blood samplings significantly reduced mean haemoglobin levels (10.9±2.0 g/dl), inducing chronic anaemia in mice, while daily administration of rHuEPO led to increase of haemoglobin levels (15.8±2.0 g/dl). Oxygenation status evaluated by a microelectrode was worsened in anaemic mice (mean pO 2 in tumour = 6.9±0.8 mmHg) and improved in rHuEPOtreated animals (mean pO 2 in tumour = 11.4±1.2 mmHg). No correlation was observed between the oxygen-sensitive probe and pimonidazole labelling results: both techniques give different but complementary information about tumour hypoxia. Areas of high pimonidazole binding and areas of high 18 F-FDG uptake superimposed well. Present results confirm that modification of haemoglobin levels leads to alteration of tumour oxygenation status. These variations were detectable using the oxygen-sensitive electrode but not the pimonidazole binding assay. The strong correlation between pimonidazole labelling and 18 F-FDG uptake suggests a positive relationship between hypoxia and increased glucose metabolism in this tumour model.

show abstract

FDG—a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer

Abstract: These results support the hypothesis that tumour hypoxia has an effect on glucose metabolism. However, other factors affecting FDG uptake may be more predominant in chronic hypoxia, and thus FDG PET cannot reliably differentiate hypoxic from normoxic tumours.

Cited by 111 publications

References 33 publications

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

¹⁸F-Fluoromisonidazole PET/CT: A Potential Tool for Predicting Primary Endocrine Therapy Resistance in Breast Cancer

Measurement of hypoxia using invasive oxygen-sensitive electrode, pimonidazole binding and 18F-FDG uptake in anaemic or erythropoietin-treated mice bearing human glioma xenografts

Contact Info

Product

Resources

About

FDG—a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer

Abstract: These results support the hypothesis that tumour hypoxia has an effect on glucose metabolism. However, other factors affecting FDG uptake may be more predominant in chronic hypoxia, and thus FDG PET cannot reliably differentiate hypoxic from normoxic tumours.

Cited by 111 publications

References 33 publications

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

18F-Fluoromisonidazole PET/CT: A Potential Tool for Predicting Primary Endocrine Therapy Resistance in Breast Cancer

Measurement of hypoxia using invasive oxygen-sensitive electrode, pimonidazole binding and 18F-FDG uptake in anaemic or erythropoietin-treated mice bearing human glioma xenografts

Contact Info

Product

Resources

About

¹⁸F-Fluoromisonidazole PET/CT: A Potential Tool for Predicting Primary Endocrine Therapy Resistance in Breast Cancer