FMISO

18F-FMISO or fluoromisonidazole is a radiopharmaceutical used for PET imaging of hypoxia. It consists of a 2-nitroimidazole molecule labelled with the positron-emitter fluorine-18.[1]

[18F]Fluoromisonidazole
Clinical data
Other names[18F]FMISO; 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole
Identifiers
IUPAC name
  • 1-(2-Nitro-imidazolyl)-3-[18F]fluoro-2-propanol
CAS Number
ChemSpider
UNII
Chemical and physical data
FormulaC6H818FN3O
Molar mass188.15 g/mol

Hypoxia is considered a negative prognostic marker for many solid tumours, and therefore an agent to detect and quantify it is highly desirable.[2] FMISO was one of the first such agents, after initial synthesis in the late 1980s.[3][4][5] It remains among the most popular agents for investigation of hypoxia imaging.[6][7][8]

Mechanism
Mechanism of the accumulation of FMISO in hypoxic tissue [9]

On entering a viable cell, the nitro group of the FMISO nitroimidazole is reduced.[10] In non-hypoxic cells, the reduced FMISO molecule can be oxidised, and therefore diffuses out of the cell to circulate freely and ultimately be excreted. In hypoxic tumour cells however this oxidation cannot take place and the FMISO molecules accumulate. Their location can then be quantitatively imaged using positron emission tomography.[9][11]

Clinical use

Large scale clinical trials with FMISO have not been carried out, however there is some evidence from small-scale early-stage imaging trials that PET-measured hypoxia (using FMISO, and the alternative radiotracer FAZA) is linked to overall survival and loco-regional control in head and neck cancer patients.[12] Similar correlations have been found in other cancers, including breast cancer and brain tumours.[10][13] Direct impacts on patient care has not yet been conclusively demonstrated however.[11]

The use of hypoxia imaging to guide radiotherapy treatments is an area of active research.[14] Despite some positive early results further research is required to characterise the specificity and sensitivity of FMISO, and exactly how hypoxia levels should influence treatment planning decisions. Similarly, hypoxia imaging could be used to screen patients before the prescription of hypoxic guided drugs. It may also be useful as a post-treatment measure of effectiveness for both radiotherapy and chemotherapy.[15][16]

Outside of oncology, there is interest in cardiac hypoxia imaging. FMISO has had limited interest for this purpose, in part due to low target-to-background contrast and long injection to imaging delays (due to slow blood clearance) requiring high injected activities.[17]

References
  1. Rajendran JG, Mankoff DA, O'Sullivan F, Peterson LM, Schwartz DL, Conrad EU, et al. (April 2004). "Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging". Clinical Cancer Research. 10 (7): 2245–52. doi:10.1158/1078-0432.ccr-0688-3. PMID 15073099.
  2. Zschaeck, S; Steinbach, J; Troost, E G (2016). "FMISO as a Biomarker for Clinical Radiation Oncology". In Baumann, M; Krause, M; Cordes, N (eds.). Molecular radio-oncology. Berlin. doi:10.1007/978-3-662-49651-0. ISBN 978-3-662-49649-7.
  3. Wadsak, W.; Mitterhauser, M. (March 2010). "Basics and principles of radiopharmaceuticals for PET/CT". European Journal of Radiology. 73 (3): 461–469. doi:10.1016/j.ejrad.2009.12.022. PMID 20181453.
  4. Jerabek, PA; Patrick, TB; Kilbourn, MR; Dischino, DD; Welch, MJ (1986). "Synthesis and biodistribution of 18F-labeled fluoronitroimidazoles: potential in vivo markers of hypoxic tissue". International Journal of Radiation Applications and Instrumentation A. 37 (7): 599–605. doi:10.1016/0883-2889(86)90079-1. PMID 3021662.
  5. Grunbaum, Z; Freauff, SJ; Krohn, KA; Wilbur, DS; Magee, S; Rasey, JS (January 1987). "Synthesis and characterization of congeners of misonidazole for imaging hypoxia". Journal of Nuclear Medicine. 28 (1): 68–75. PMID 3794812.
  6. Tamaki, Nagara; Hirata, Kenji (August 2016). "Tumor hypoxia: a new PET imaging biomarker in clinical oncology". International Journal of Clinical Oncology. 21 (4): 619–625. doi:10.1007/s10147-015-0920-6. PMID 26577447. S2CID 30098261.
  7. Fleming, I N; Manavaki, R; Blower, P J; West, C; Williams, K J; Harris, A L; Domarkas, J; Lord, S; Baldry, C; Gilbert, F J (January 2015). "Imaging tumour hypoxia with positron emission tomography". British Journal of Cancer. 112 (2): 238–250. doi:10.1038/bjc.2014.610. PMC 4453462. PMID 25514380.
  8. Kelada, Olivia J.; Carlson, David J. (April 2014). "Molecular Imaging of Tumor Hypoxia with Positron Emission Tomography". Radiation Research. 181 (4): 335–349. Bibcode:2014RadR..181..335K. doi:10.1667/RR13590.1. PMC 5555673. PMID 24673257.
  9. Masaki, Yukiko; Shimizu, Yoichi; Yoshioka, Takeshi; Tanaka, Yukari; Nishijima, Ken-ichi; Zhao, Songji; Higashino, Kenichi; Sakamoto, Shingo; Numata, Yoshito; Yamaguchi, Yoshitaka; Tamaki, Nagara; Kuge, Yuji (December 2015). "The accumulation mechanism of the hypoxia imaging probe "FMISO" by imaging mass spectrometry: possible involvement of low-molecular metabolites". Scientific Reports. 5 (1): 16802. Bibcode:2015NatSR...516802M. doi:10.1038/srep16802. PMC 4652161. PMID 26582591.
  10. Drake, Lindsey R.; Hillmer, Ansel T.; Cai, Zhengxin (28 January 2020). "Approaches to PET Imaging of Glioblastoma". Molecules. 25 (3): 568. doi:10.3390/molecules25030568. PMC 7037643. PMID 32012954.
  11. Sorace, Anna G.; Elkassem, Asser A.; Galgano, Samuel J.; Lapi, Suzanne E.; Larimer, Benjamin M.; Partridge, Savannah C.; Quarles, C. Chad; Reeves, Kirsten; Napier, Tiara S.; Song, Patrick N.; Yankeelov, Thomas E.; Woodard, Stefanie; Smith, Andrew D. (November 2020). "Imaging for Response Assessment in Cancer Clinical Trials". Seminars in Nuclear Medicine. 50 (6): 488–504. doi:10.1053/j.semnuclmed.2020.05.001. PMC 7573201. PMID 33059819.
  12. Zschaeck, Sebastian; Löck, Steffen; Hofheinz, Frank; Zips, Daniel; Saksø Mortensen, Lise; Zöphel, Klaus; Troost, Esther G.C.; Boeke, Simon; Saksø, Mette; Mönnich, David; Seidlitz, Annekatrin; Johansen, Jørgen; Skripcak, Tomas; Gregoire, Vincent; Overgaard, Jens; Baumann, Michael; Krause, Mechthild (August 2020). "Individual patient data meta-analysis of FMISO and FAZA hypoxia PET scans from head and neck cancer patients undergoing definitive radio-chemotherapy". Radiotherapy and Oncology. 149: 189–196. doi:10.1016/j.radonc.2020.05.022. PMID 32417350.
  13. Inubushi, Masayuki; Tatsumi, Mitsuaki; Yamamoto, Yuka; Kato, Katsuhiko; Tsujikawa, Tetsuya; Nishii, Ryuichi (November 2018). "European research trends in nuclear medicine". Annals of Nuclear Medicine. 32 (9): 579–582. doi:10.1007/s12149-018-1303-7. PMC 6208859. PMID 30242670.
  14. Lopes, Susana; Ferreira, Sara; Caetano, Marco (June 2021). "PET/CT in the Evaluation of Hypoxia for Radiotherapy Planning in Head and Neck Tumors: Systematic Literature Review". Journal of Nuclear Medicine Technology. 49 (2): 107–113. doi:10.2967/jnmt.120.249540. PMID 33361182.
  15. Xu, Zuoyu; Li, Xiao-Feng; Zou, Hongyan; Sun, Xilin; Shen, Baozhong (7 November 2017). "18F-Fluoromisonidazole in tumor hypoxia imaging". Oncotarget. 8 (55): 94969–94979. doi:10.18632/oncotarget.21662. PMC 5706929. PMID 29212283.
  16. Marcus, Charles; Subramaniam, Rathan M. (January 2021). "Role of Non-FDG-PET/CT in Head and Neck Cancer". Seminars in Nuclear Medicine. 51 (1): 68–78. doi:10.1053/j.semnuclmed.2020.07.008. PMID 33246541.
  17. Pell, Victoria R.; Baark, Friedrich; Mota, Filipa; Clark, James E.; Southworth, Richard (March 2018). "PET Imaging of Cardiac Hypoxia: Hitting Hypoxia Where It Hurts". Current Cardiovascular Imaging Reports. 11 (3): 7. doi:10.1007/s12410-018-9447-3. PMC 5830463. PMID 29515752.
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