EF5 binding and clinical outcome in human soft tissue sarcomas

Evans, Sydney M.; Fraker, Douglas L.; Hahn, Stephen M.; Gleason, Kristen D; Jenkins, W. Timothy; Jenkins, Kevin W.; Hwang, Wei Ting; Zhang, Paul; Mick, Rosemarie; Koch, Cameron J.

doi:10.1016/j.ijrobp.2005.05.068

Cited by 51 publications

(34 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that certain agents will perform differently in specific tumor types. One clear advantage of 18 F-EF5 is that it is the same molecule as EF5, which has been used extensively to study hypoxia in numerous clinical and preclinical settings (17)(18)(19)(20)22,31,32,38). It is our goal to compare results from studies in which EF5-based immunohistochemical images were compared with PET 18 F-EF5 images.…”

Section: Discussionmentioning

confidence: 99%

“…18 F-fluoromisonidazole ( 18 F-FMISO) (13), 18 F-fluoroerythronitroimidazole (14), 18 F-fluoroazomycin arabinoside (15), and 18 F-fluoroetanidazole have been used with varying success as PET probes for hypoxia imaging, but only 18 F-FMISO is available in more than a few of the centers worldwide. However, a new group of etanidazole-based compounds, >2-(2-nitroimidazol-1 H-y)-N-(3-flouropropyl)acetamide (EF1) (16), 2-(2-nitroimidazol-1 H-y)-N-(3,3,3-tryflouropropyl)acetamide (EF3), and EF5 (17)(18)(19), has been developed both as biopsy-based (20) and as PET-based agents, and 18 F-EF5 has been synthesized by Dolbier et al (17) as well as at our center.…”

mentioning

confidence: 99%

See 1 more Smart Citation

¹⁸F-EF5: A New PET Tracer for Imaging Hypoxia in Head and Neck Cancer

Komar¹,

Seppänen²,

Eskola³

et al. 2008

J Nucl Med

Self Cite

173

118

View full text Add to dashboard Cite

The aim of this study was to evaluate 2-(2-nitro-1 H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) labeled with 18 F-fluorine to image hypoxia in patients with squamous cell carcinoma of the head and neck (HNSCC). Methods: Fifteen patients with HNSCC were studied. Measurement of tumor blood flow was followed by an 18 F-EF5 PET/CT scan. On a separate day, 18 F-FDG PET/CT was performed to determine the metabolically active tumor volume. In 6 patients, dynamic 18 F-EF5 images of the head and neck area were acquired, followed by static images acquired at 1, 2, and 3 h after injection. In the remaining 9 patients, only static images were obtained. 18 F-EF5 uptake in tumors was compared with that in neck muscle, and the 18 F-EF5 findings were correlated with the 18 F-FDG PET/CT studies. Results: A total of 13 primary tumors and 5 lymph node metastases were evaluated for their uptake of 18 F-EF5. The median tumor-to-muscle 18 F-EF5 uptake ratio (T/M) increased over time and was 1.38 (range, 1.1-3.2) 3 h after tracer injection. The median blood flow in tumors was 36.7 mL/100 g/min (range, 23.3-78.6 mL/100 g/min). Voxel-by-voxel analysis of coregistered blood flow and 18 F-EF5 images revealed a distinct pattern, resulting in a T/M of 1.5 at 3 h to be chosen as a cutoff for clinically significant hypoxia. Fourteen of 18 tumors (78%) had subvolumes within the metabolically active tumor volumes with T/M greater than or equal to 1.5. Conclusion: On the basis of these data, the potential of 18 F-EF5 to detect hypoxia in HNSCC is encouraging. Further development of 18 F-EF5 for eventual targeting of antihypoxia therapies is warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

¹⁸F-EF5: A New PET Tracer for Imaging Hypoxia in Head and Neck Cancer

Komar¹,

Seppänen²,

Eskola³

et al. 2008

J Nucl Med

Self Cite

173

118

View full text Add to dashboard Cite

show abstract

“…In a recent clinical study of head and neck tumors, high pimonidazole binding correlated with poor treatment outcome (12). This has also been observed with EF5 in soft tissue sarcomas (49). In the head and neck study, the benefit of hypoxiabased intervention with ARCON [accelerated radiotherapy combined with carbogen (95% O 2 and 5% CO 2 ) and nicotinamide] was confirmed since the predictive power of pimonidazole binding disappeared in the ARCON-treated group (12).…”

Section: Predictive Value Of Pimonidazolementioning

confidence: 69%

“…To achieve this, further understanding of tumor cell hypoxia in relation to other clinically relevant parameters is necessary (46). Although several methods exist for detection of hypoxia, only the Eppendorf electrode (9,47,48) and the bioreductive hypoxic cell markers pimonidazole and EF5 (12,49) have shown prognostic significance in clinical studies or have been able to discriminate responders from nonresponders on a group basis.…”

Section: Detection Of Hypoxiamentioning

confidence: 99%

“…This demonstrates the limitations of the Eppendorf method at the microregional and cellular levels (50). The hypoxic fractions determined using pimonidazole or EF5 measured in tumor biopsies predicted outcome for patients treated with radiotherapy (12,49) and may therefore become a new gold standard for assays detecting hypoxia at the cellular level.…”

Section: Predictive Value Of Pimonidazolementioning

confidence: 99%

See 1 more Smart Citation

Dynamics of Tumor Hypoxia Measured with Bioreductive Hypoxic Cell Markers

et al. 2007

View full text Add to dashboard Cite

Hypoxic cells are common in tumors and contribute to malignant progression, distant metastasis and resistance to radiotherapy. It is well known that tumors are heterogeneous with respect to the levels and duration of hypoxia. Several strategies, including high-oxygen-content gas breathing, radiosensitizers and hypoxic cytotoxins, have been developed to overcome hypoxia-mediated radioresistance. However, with these strategies, an increased tumor control rate is often accompanied by more severe side effects. Consequently, development of assays for prediction of tumor response and early monitoring of treatment responses could reduce both overand undertreatment, thereby avoiding unnecessary side effects. The purpose of this review is to discuss different assays for measurement of hypoxia that can be used to detect changes in oxygen tension. The main focus is on exogenous bioreductive hypoxia markers (2-nitroimidazoles) such as pimonidazole, CCI-103F, EF5 and F-misonidazole. These are specifically reduced and bind to macromolecules in viable hypoxic cells. A number of these bioreductive drugs are approved for clinical use and can be detected with methods ranging from noninvasive PET imaging (low resolution) to microscopic imaging of tumor sections (high resolution). If the latter are stained for multiple markers, hypoxia can be analyzed in relation to different microenvironmental parameters such as vasculature, proliferation and endogenous hypoxia-related markers, for instance HIF1␣ and CA-IX. In addition, temporal and spatial changes in hypoxia can be analyzed by consecutive injection of two different hypoxia markers. Therefore, bioreductive exogenous hypoxia markers are promising as tools for development of predictive assays or as tools for early treatment monitoring and validation of potential endogenous hypoxia markers. ᭧

show abstract

Nano versus Molecular: Optical Imaging Approaches to Detect and Monitor Tumor Hypoxia

Cheng

Zheng

2020

Adv Healthcare Materials

View full text Add to dashboard Cite

Hypoxia is a ubiquitous feature of solid tumors, which plays a key role in tumor angiogenesis and resistance development. Conventional hypoxia detection methods lack continuous functional detection and are generally less suitable for dynamic hypoxia measurement. Optical sensors hereby provide a unique opportunity to noninvasively image hypoxia with high spatiotemporal resolution and enable real‐time detection. Therefore, these approaches can provide a valuable tool for personalized treatment planning against this hallmark of aggressive cancers. Many small optical molecular probes can enable analyte triggered response and their photophysical properties can also be fine‐tuned through structural modification. On the other hand, optical nanoprobes can acquire unique intrinsic optical properties through nanoconfinement as well as enable simultaneous multimodal imaging and drug delivery. Furthermore, nanoprobes provide biological advantages such as improving bioavailability and systemic delivery of the sensor to enhance bioavailability. This review provides a comprehensive overview of the physical, chemical, and biological analytes for cancer hypoxia detection and focuses on discussing the latest nano‐ and molecular developments in various optical imaging approaches (fluorescence, phosphorescence, and photoacoustic) in vivo. Finally, this review concludes with a perspective toward the potentials of these optical imaging approaches in hypoxia detection and the challenges with molecular and nanotechnology design strategies.

show abstract

EF5 binding and clinical outcome in human soft tissue sarcomas

Cited by 51 publications

References 21 publications

¹⁸F-EF5: A New PET Tracer for Imaging Hypoxia in Head and Neck Cancer

¹⁸F-EF5: A New PET Tracer for Imaging Hypoxia in Head and Neck Cancer

Dynamics of Tumor Hypoxia Measured with Bioreductive Hypoxic Cell Markers

Nano versus Molecular: Optical Imaging Approaches to Detect and Monitor Tumor Hypoxia

Contact Info

Product

Resources

About

EF5 binding and clinical outcome in human soft tissue sarcomas

Cited by 51 publications

References 21 publications

18F-EF5: A New PET Tracer for Imaging Hypoxia in Head and Neck Cancer

18F-EF5: A New PET Tracer for Imaging Hypoxia in Head and Neck Cancer

Dynamics of Tumor Hypoxia Measured with Bioreductive Hypoxic Cell Markers

Nano versus Molecular: Optical Imaging Approaches to Detect and Monitor Tumor Hypoxia

Contact Info

Product

Resources

About

¹⁸F-EF5: A New PET Tracer for Imaging Hypoxia in Head and Neck Cancer

¹⁸F-EF5: A New PET Tracer for Imaging Hypoxia in Head and Neck Cancer