Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging

Minn, Heikki; Clavo, Anaira C.; Wahl, Richard L.

doi:10.1016/s0969-8051(96)00134-5

Cited by 68 publications

(33 citation statements)

References 21 publications

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“…Although FDG-PET has been proposed as a surrogate marker for hypoxia (31), the heterogeneous cellular response to hypoxia results in significant differences between hypoxia and glycolysis (20,32,33). This difference is apparent in Fig.…”

Section: Discussionmentioning

confidence: 99%

Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole Positron Emission Tomography in Head and Neck Cancer

Rajendran

Schwartz

O’Sullivan

et al. 2006

Clinical Cancer Research

319

238

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Purpose: Advanced head and neck cancer shows hypoxia that results in biological changes to make the tumor cells more aggressive and less responsive to treatment resulting in poor survival. [F-18] fluoromisonidazole (FMISO) positron emission tomography (PET) has the ability to noninvasively quantify regional hypoxia. We investigated the prognostic effect of pretherapy FMISO-PETon survival in head and neck cancer. Experimental Design: Seventy-three patients with head and neck cancer had pretherapy FMISO-PETand 53 also had fluorodeoxyglucose (FDG) PETunder a research protocol from April 1994 to April 2004. Results: Significant hypoxia was identified in 58 patients (79%). The mean FMISO tumor/ blood max (T/B max ) was 1.6 and the mean hypoxic volume (HV) was 40.2 mL. There were 28 deaths in the follow-up period. Mean FDG standard uptake value (SUV) max was 10.8.The median time for follow-up was 72 weeks. In a univariate analysis,T/B max (P = 0.002), HV (P = 0.04), and the presence of nodes (P = 0.01) were strong independent predictors. In a multivariate analysis, including FDG SUV max , no variable was predictive at P < 0.05. When FDG SUV max was removed from the model (resulting in n = 73 with 28 events), nodal status and T/B max (or HV) were both highly predictive (P = 0.02, 0.006 for node andT/B max , respectively; P = 0.02 and 0.001for node and HV, respectively).Conclusions: Pretherapy FMISO uptake shows a strong trend to be an independent prognostic measure in head and neck cancer.

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Section: Discussionmentioning

confidence: 99%

Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole Positron Emission Tomography in Head and Neck Cancer

Rajendran

Schwartz

O’Sullivan

et al. 2006

Clinical Cancer Research

319

238

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“…The magnitude of 18 F-FDG uptake has been shown to be an important prognostic factor independent of established prognostic factors in patients with tumors such as lung cancer and breast cancer (29,30). Preclinical studies of human tumor cell lines and clinical data suggest that hypoxia plays a role in tumor 18 F-FDG uptake (31)(32)(33)(34)(35). It has been shown that hypoxia increases the level of hypoxia-inducible factor 1a, which increases the expression of glycolytic enzymes and glucose transport proteins (36).…”

Section: Discussionmentioning

confidence: 99%

Assessing Tumor Hypoxia in Cervical Cancer by PET with ⁶⁰Cu-Labeled Diacetyl-Bis(N⁴-Methylthiosemicarbazone)

Grigsby²,

et al. 2008

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Tumor hypoxia indicates a poor prognosis. This study was undertaken to confirm our prior pilot results showing that pretreatment tumor hypoxia demonstrated by PET with 60 Cu-labeled diacetylbis(N 4 -methylthiosemicarbazone) ( 60 Cu-ATSM) is a biomarker of poor prognosis in patients with cervical cancer. Thirty-eight women with biopsy-proved cervical cancer underwent 60 Cu-ATSM PET before the initiation of radiotherapy and chemotherapy. 60 Cu-ATSM uptake was evaluated semiquantitatively as the tumor-to-muscle activity ratio (T/M). A log-rank test was used to determine the cutoff uptake value that was strongly predictive of prognosis. All patients also underwent clinical PET with 18 F-FDG before the institution of therapy. The PET results were correlated with clinical follow-up. Tumor 60 Cu-ATSM uptake was inversely related to progression-free survival and cause-specific survival (P 5 0.006 and P 5 0.04, respectively, as determined by the log-rank test). We found that a T/M threshold of 3.5 best discriminated patients likely to develop a recurrence from those unlikely to develop a recurrence; the 3-y progression-free survival of patients with normoxic tumors (as defined by T/M of #3.5) was 71%, and that of patients with hypoxic tumors (T/M of .3.5) was 28% (P 5 0.01). Tumor 18 F-FDG uptake did not correlate with 60 Cu-ATSM uptake, and there was no significant difference in tumor 18 F-FDG uptake between patients with hypoxic tumors and those with normoxic tumors (P 5 0.9). Pretherapy 60 Cu-ATSM PET provides clinically relevant information about tumor oxygenation that is predictive of outcome in patients with cervical cancer. Tumorhypoxi a has been shown to be important in determining the response to therapy in solid tumors, including cervical cancer. Hypoxic cells are more resistant to killing by ionizing radiation and chemotherapy, more likely to be locally invasive and to metastasize, more resistant to apoptosis, and more genetically unstable (1,2). Thus, because of the importance of tumor hypoxia, considerable research has focused on developing methods to measure hypoxia reliably as well as on strategies for improving tumor oxygenation or ameliorating the effects of hypoxia. Considering the new therapeutic agents that target hypoxia, identifying a practical method for detecting hypoxia becomes highly important. In general, a method suitable for routine clinical application needs to be practical, readily available, and reliable. Polarographic oxygen electrodes (Eppendorf GmbH) made it possible to measure tumor oxygenation, which produced clinically relevant information. Early clinical studies with oxygen electrodes were very promising and demonstrated that hypoxic tumors, including cervical tumors, respond poorly to radiation therapy (3-10). However, the oxygen electrode method is invasive, technically demanding, useful only for studying tumors accessible to electrode placement, and subject to sampling errors. Thus, this method is not considered clinically practical.Recently, noninvasive imaging methods, particu...

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“…Hypoxia-inducible factor 1α, which is overexpressed in response to hypoxia, is the primary transcription factor mediating a number of physiological and biological changes that include aerobic glycolysis and slowing down of proliferation [53]. Under hypoxic conditions in vitro, increased FDG uptake by cancer cells has been reported [54]. In vivo results from Kubota and coworkers in rats using autoradiograms [47] and PET data from Rajendran et al in malignant human cancers [55] showed similar findings, suggesting a compensatory mechanism for the reduced delivery of glucose to the hypoxic tumour tissue by augmented tissue extraction owing to elevated glucose-transporter activity under hypoxia.…”

Section: Discussionmentioning

confidence: 99%

NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours

Wyss

Honer

Schubiger

et al. 2005

Eur J Nucl Med Mol Imaging

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Abstract. Purpose: The purpose of this study was to assess the potential and utility of ultra-high-resolution hypoxia imaging in various murine tumour models using the established hypoxia PET tracer [ 18 F] FMISO PET imaging allowed clear-cut visualisation of the tumours. Inter-and intratumoural heterogeneity of tracer uptake was evident. In addition to average TMRR (tumour-to-muscle retention ratio including all voxels in a volume of interest (VOI)), the parameters TMRR 75% and TMRR 5 (tumour-to-muscle retention ratio including voxels of 75% or more of the maximum radioactivity in a VOI and the five hottest pixels, respectively) also served as measures for quantifying the heterogeneous [

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Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging

Cited by 68 publications

References 21 publications

Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole Positron Emission Tomography in Head and Neck Cancer

Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole Positron Emission Tomography in Head and Neck Cancer

Assessing Tumor Hypoxia in Cervical Cancer by PET with ⁶⁰Cu-Labeled Diacetyl-Bis(N⁴-Methylthiosemicarbazone)

NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours

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Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging

Cited by 68 publications

References 21 publications

Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole Positron Emission Tomography in Head and Neck Cancer

Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole Positron Emission Tomography in Head and Neck Cancer

Assessing Tumor Hypoxia in Cervical Cancer by PET with 60Cu-Labeled Diacetyl-Bis(N4-Methylthiosemicarbazone)

NanoPET imaging of [18F]fluoromisonidazole uptake in experimental mouse tumours

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Assessing Tumor Hypoxia in Cervical Cancer by PET with ⁶⁰Cu-Labeled Diacetyl-Bis(N⁴-Methylthiosemicarbazone)