18F-EF5

For other uses, see EF-5.

EF5 is a nitroimidazole derivative used in oncology research.^[1] Due to its similarity in chemical structure to etanidazole, EF5 binds in cells displaying hypoxia.^[2]

18F-EF5

Names
Preferred IUPAC name 2-(2-Nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide
Other names NSC-684681; EF-5
Identifiers
CAS Number	152721-37-4 Y
3D model (JSmol)	Interactive image
ChemSpider	344807 Y
PubChem CID	389053
UNII	383HJ2T87O Y
CompTox Dashboard (EPA)	DTXSID10165114
InChI InChI=1S/C8H7F5N4O3/c9-7(10,8(11,12)13)4-15-5(18)3-16-2-1-14-6(16)17(19)20/h1-2H,3-4H2,(H,15,18) Y Key: JGGDSDPOPRWSCX-UHFFFAOYSA-N Y
SMILES O=[N+]([O-])c1nccn1CC(=O)NCC(F)(F)C(F)(F)F
Properties
Chemical formula	C8H7F5N4O3
Molar mass	302.161 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Non-labeled EF5 has been extensively used in immunohistochemical studies for several years and its hypoxia specificity has been comprehensively evaluated^[3][4] The ¹⁸F-radiolabeled derivative of EF5 is being studied for its possibility to be used in positron emission tomography (PET) to detect low levels of oxygen in brain tumors and several other malignant tumors.^[5] This can help show how a tumor will respond to treatment.

Targeting tumor hypoxia in cancer treatment aims to overcome radiotherapy resistance of hypoxic tumors. Thus, a major clinical implication for ¹⁸F-EF5-PET imaging is expected to be guiding of radiotherapy dose modulation. Clinical studies on ¹⁸F-EF5-PET/CT imaging have indicated clinically acceptable biodistribution and dosimetric profile,^[6] and in head and neck cancer also favorable imaging characteristics,^[7] prognostic value^[8] and repeatability.^[9] A recent 18F-EF5-PET/MR study showed promising potential in detecting tumor hypoxia in cervical cancer.^[10] However, ¹⁸F-EF5-PET/CT is not feasible in imaging of ovarian cancer due to physiological intra-abdominal ¹⁸F-EF5-accumulation.^[11] Further studies evaluating the clinical use of ¹⁸F-EF5 PET imaging in head and neck cancer are ongoing.

References

1. Evans SM, Fraker D, Hahn SM, Gleason K, Jenkins WT, Jenkins K, et al. (March 2006). "EF5 binding and clinical outcome in human soft tissue sarcomas". International Journal of Radiation Oncology, Biology, Physics. 64 (3): 922–7. doi:10.1016/j.ijrobp.2005.05.068. PMID 16458778.
2. Lord EM, Harwell L, Koch CJ (December 1993). "Detection of hypoxic cells by monoclonal antibody recognizing 2-nitroimidazole adducts". Cancer Research. 53 (23): 5721–6. PMID 8242628.
3. Koch CJ, Evans SM (March 2015). "Optimizing hypoxia detection and treatment strategies". Seminars in Nuclear Medicine. 45 (2): 163–76. doi:10.1053/j.semnuclmed.2014.10.004. PMC 4365940. PMID 25704388.
4. Koch CJ (2002). "[1] Measurement of absolute oxygen levels in cells and tissues using oxygen sensors and 2-nitroimidazole EF5". Measurement of absolute oxygen levels in cells and tissues using oxygen sensors and 2-nitroimidazole EF5. Methods in Enzymology. Vol. 352. Elsevier. pp. 3–31. doi:10.1016/s0076-6879(02)52003-6. ISBN 978-0-12-182255-2. PMID 12125356.
5. Ziemer LS, Evans SM, Kachur AV, Shuman AL, Cardi CA, Jenkins WT, et al. (February 2003). "Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole 18F-EF5". European Journal of Nuclear Medicine and Molecular Imaging. 30 (2): 259–66. doi:10.1007/s00259-002-1037-5. PMID 12552344. S2CID 22002592.
6. Lin LL, Silvoniemi A, Stubbs JB, Rengan R, Suilamo S, Solin O, et al. (September 2012). "Radiation dosimetry and biodistribution of the hypoxia tracer (18)F-EF5 in oncologic patients". Cancer Biotherapy & Radiopharmaceuticals. 27 (7): 412–9. doi:10.1089/cbr.2011.1130. PMID 22897720.
7. Komar G, Seppänen M, Eskola O, Lindholm P, Grönroos TJ, Forsback S, et al. (December 2008). "18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer". Journal of Nuclear Medicine. 49 (12): 1944–51. doi:10.2967/jnumed.108.053785. PMID 18997048. S2CID 16561341.
8. Komar G, Lehtiö K, Seppänen M, Eskola O, Levola H, Lindholm P, et al. (November 2014). "Prognostic value of tumour blood flow, [¹⁸F]EF5 and [¹⁸F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy". European Journal of Nuclear Medicine and Molecular Imaging. 41 (11): 2042–50. doi:10.1007/s00259-014-2818-3. PMID 24898846. S2CID 6276936.
9. Silvoniemi A, Suilamo S, Laitinen T, Forsback S, Löyttyniemi E, Vaittinen S, et al. (February 2018). "Repeatability of tumour hypoxia imaging using [¹⁸F]EF5 PET/CT in head and neck cancer". European Journal of Nuclear Medicine and Molecular Imaging. 45 (2): 161–169. doi:10.1007/s00259-017-3857-3. PMC 5745570. PMID 29075831.
10. Narva, Sara I.; Seppänen, Marko P.; Raiko, Juho R.H.; Forsback, Sarita J.; Orte, Katri J.; Virtanen, Johanna M.; Hynninen, Johanna; Hietanen, Sakari (December 2021). "Imaging of Tumor Hypoxia With 18F-EF5 PET/MRI in Cervical Cancer". Clinical Nuclear Medicine. 46 (12): 952–957. doi:10.1097/RLU.0000000000003914. ISSN 1536-0229. PMID 34619699.
11. Laasik M, Hynninen J, Forsback S, Noponen T, Seppänen M, Hietanen S (September 2020). "The feasibility of [¹⁸F]EF5-PET/CT to image hypoxia in ovarian tumors: a clinical study". EJNMMI Research. 10 (1): 103. doi:10.1186/s13550-020-00689-z. PMC 7483702. PMID 32910291.