FMISO

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[18F]Fluoromisonidazole
18F-Fluoromisonidazole.svg
Clinical data
Other names[18F]FMISO; 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole
Identifiers
  • 1-(2-Nitro-imidazolyl)-3-[18F]fluoro-2-propanol
CAS Number
ChemSpider
UNII
Chemical and physical data
Formula C6H818FN3O
Molar mass 188.15g/mol

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]

Contents

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 FMISO hypoxia accumulation mechanism.png
Mechanism of the accumulation of FMISO in hypoxic tissue

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]

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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): 2245–2252. doi: 10.1158/1078-0432.ccr-0688-3 . PMID   15073099.
  2. ↑ Zschaeck S, Steinbach J, Troost EG (2016). "FMISO as a Biomarker for Clinical Radiation Oncology". In Baumann M, Krause M, Cordes N (eds.). Molecular radio-oncology. Recent Results in Cancer Research. Vol. 198. Berlin: Springer. pp. 189–201. 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. Part A, Applied Radiation and Isotopes. 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 N, Hirata K (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 IN, Manavaki R, Blower PJ, West C, Williams KJ, Harris AL, et al. (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 OJ, Carlson DJ (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. 1 2 Masaki Y, Shimizu Y, Yoshioka T, Tanaka Y, Nishijima K, Zhao S, et al. (November 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. 1 2 Drake LR, Hillmer AT, Cai Z (January 2020). "Approaches to PET Imaging of Glioblastoma". Molecules. 25 (3): 568. doi: 10.3390/molecules25030568 . PMC   7037643 . PMID   32012954.
  11. 1 2 Sorace AG, Elkassem AA, Galgano SJ, Lapi SE, Larimer BM, Partridge SC, et al. (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 S, Löck S, Hofheinz F, Zips D, Saksø Mortensen L, Zöphel K, et al. (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. S2CID   218678537.
  13. ↑ Inubushi M, Tatsumi M, Yamamoto Y, Kato K, Tsujikawa T, Nishii R (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 S, Ferreira S, Caetano M (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 . hdl: 10400.21/13161 . PMID   33361182.
  15. ↑ Xu Z, Li XF, Zou H, Sun X, Shen B (November 2017). "18F-Fluoromisonidazole in tumor hypoxia imaging". Oncotarget. 8 (55): 94969–94979. doi: 10.18632/oncotarget.21662 . PMC   5706929 . PMID   29212283.
  16. ↑ Marcus C, Subramaniam RM (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. S2CID   225405293.
  17. ↑ Pell VR, Baark F, Mota F, Clark JE, Southworth R (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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