Jump to content

FMISO: Difference between revisions

Add links
From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Add CAS Common chemistry number and InChIKey from that CAS
Significantly expanding
Line 40: Line 40:
| DrugBank =
| DrugBank =
| ChemSpiderID = 396524
| ChemSpiderID = 396524
| InChIKey = HIIJZYSUEJYLMX-JZRMKITLSA-N
| StdInChIKey = HIIJZYSUEJYLMX-JZRMKITLSA-N
| synonyms = [18F]FMISO; 1''H''-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole
| synonyms = [18F]FMISO; 1''H''-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole
<!-- Chemical data -->
<!-- Chemical data -->
Line 47: Line 47:
}}
}}


'''FMISO''' or '''fluoromisonidazole''' is used as a [[Positron emission tomography|PET]] radiotracer for imaging [[Hypoxia (medical)|hypoxia]] when labeled with [[fluorine-18]].<ref>{{cite journal | vauthors = Rajendran JG, Mankoff DA, O'Sullivan F, Peterson LM, Schwartz DL, Conrad EU, Spence AM, Muzi M, Farwell DG, Krohn KA | display-authors = 6 | title = Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging | journal = Clinical Cancer Research | volume = 10 | issue = 7 | pages = 2245–52 | date = April 2004 | pmid = 15073099 | doi = 10.1158/1078-0432.ccr-0688-3 | doi-access = free }}</ref>
'''<sup>18</sup>F-FMISO''' or '''fluoromisonidazole''' is a [[radiopharmaceutical]] used for [[Positron emission tomography|PET]] imaging of [[Hypoxia (medical)|hypoxia]]. It consists of a 2-[[nitroimidazole]] molecule labelled with the positron-emitter [[fluorine-18]].<ref>{{cite journal | vauthors = Rajendran JG, Mankoff DA, O'Sullivan F, Peterson LM, Schwartz DL, Conrad EU, Spence AM, Muzi M, Farwell DG, Krohn KA | display-authors = 6 | title = Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging | journal = Clinical Cancer Research | volume = 10 | issue = 7 | pages = 2245–52 | date = April 2004 | pmid = 15073099 | doi = 10.1158/1078-0432.ccr-0688-3 | doi-access = free }}</ref>

Hypoxia is considered a negative [[Prognosis marker|prognostic marker]] for many [[solid tumours]], and therefore an agent to detect and quantify it is highly desirable.<ref>{{cite book |last1=Zschaeck |first1=S |last2=Steinbach |first2=J |last3=Troost |first3=E G |editor1-last=Baumann |editor1-first=M |editor2-last=Krause |editor2-first=M |editor3-last=Cordes |editor3-first=N |title=Molecular radio-oncology |date=2016 |location=Berlin |isbn=978-3-662-49649-7 |chapter=FMISO as a Biomarker for Clinical Radiation Oncology|chapter-url=https://link.springer.com/chapter/10.1007%2F978-3-662-49651-0_10|doi=10.1007/978-3-662-49651-0}}</ref> FMISO was one of the first such agents, first synthesised in the late 1980s.<ref>{{cite journal |last1=Wadsak |first1=W. |last2=Mitterhauser |first2=M. |title=Basics and principles of radiopharmaceuticals for PET/CT |journal=European Journal of Radiology |date=March 2010 |volume=73 |issue=3 |pages=461–469 |doi=10.1016/j.ejrad.2009.12.022}}</ref><ref>{{cite journal |last1=Jerabek |first1=PA |last2=Patrick |first2=TB |last3=Kilbourn |first3=MR |last4=Dischino |first4=DD |last5=Welch |first5=MJ |title=Synthesis and biodistribution of 18F-labeled fluoronitroimidazoles: potential in vivo markers of hypoxic tissue. |journal=International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes |date=1986 |volume=37 |issue=7 |pages=599-605 |doi=10.1016/0883-2889(86)90079-1 |pmid=3021662}}</ref><ref>{{cite journal |last1=Grunbaum |first1=Z |last2=Freauff |first2=SJ |last3=Krohn |first3=KA |last4=Wilbur |first4=DS |last5=Magee |first5=S |last6=Rasey |first6=JS |title=Synthesis and characterization of congeners of misonidazole for imaging hypoxia. |journal=Journal of nuclear medicine : official publication, Society of Nuclear Medicine |date=January 1987 |volume=28 |issue=1 |pages=68-75 |pmid=3794812}}</ref> It remains among the most popular agents for investigation of hypoxia imaging.<ref>{{cite journal |last1=Tamaki |first1=Nagara |last2=Hirata |first2=Kenji |title=Tumor hypoxia: a new PET imaging biomarker in clinical oncology |journal=International Journal of Clinical Oncology |date=August 2016 |volume=21 |issue=4 |pages=619–625 |doi=10.1007/s10147-015-0920-6 |pmid=26577447}}</ref><ref>{{cite journal |last1=Fleming |first1=I N |last2=Manavaki |first2=R |last3=Blower |first3=P J |last4=West |first4=C |last5=Williams |first5=K J |last6=Harris |first6=A L |last7=Domarkas |first7=J |last8=Lord |first8=S |last9=Baldry |first9=C |last10=Gilbert |first10=F J |title=Imaging tumour hypoxia with positron emission tomography |journal=British Journal of Cancer |date=January 2015 |volume=112 |issue=2 |pages=238–250 |doi=10.1038/bjc.2014.610 |pmc=4453462|doi-access=free}}</ref><ref>{{cite journal |last1=Kelada |first1=Olivia J. |last2=Carlson |first2=David J. |title=Molecular Imaging of Tumor Hypoxia with Positron Emission Tomography |journal=Radiation Research |date=April 2014 |volume=181 |issue=4 |pages=335–349 |doi=10.1667/RR13590.1 |pmc=5555673}}</ref>

==Mechanism==
[[File:FMISO hypoxia accumulation mechanism.png|thumb|left|alt=Chemical changes involved in the reduction and accumulation of FMISO in hypoxic tissue regions|Mechanism of the accumulation of FMISO in hypoxic tissue <ref name="MasakiMechanism15" />]]
On entering a viable cell, the [[Nitro compound|nitro group]] of the FMISO nitroimidazole is [[Reduction (chemistry)|reduced]].<ref name="Drake20">{{cite journal |last1=Drake |first1=Lindsey R. |last2=Hillmer |first2=Ansel T. |last3=Cai |first3=Zhengxin |title=Approaches to PET Imaging of Glioblastoma |journal=Molecules |date=28 January 2020 |volume=25 |issue=3 |pages=568 |doi=10.3390/molecules25030568 |pmc=7037643|doi-access=free}}</ref> In non-hypoxic cells, the reduced FMISO molecule can be [[oxidised]], and therefore [[diffuse]]s out of the cell to circulate freely and ultimately be excreted. In [[tumour hypoxia|hypoxic tumour]] cells however this oxidation cannot take place and the FMISO molecules accumulate. Their location can then be [[Quantification (science)|quantitatively]] imaged using [[positron emission tomography]].<ref name="MasakiMechanism15">{{cite journal |last1=Masaki |first1=Yukiko |last2=Shimizu |first2=Yoichi |last3=Yoshioka |first3=Takeshi |last4=Tanaka |first4=Yukari |last5=Nishijima |first5=Ken-ichi |last6=Zhao |first6=Songji |last7=Higashino |first7=Kenichi |last8=Sakamoto |first8=Shingo |last9=Numata |first9=Yoshito |last10=Yamaguchi |first10=Yoshitaka |last11=Tamaki |first11=Nagara |last12=Kuge |first12=Yuji |title=The accumulation mechanism of the hypoxia imaging probe “FMISO” by imaging mass spectrometry: possible involvement of low-molecular metabolites |journal=Scientific Reports |date=December 2015 |volume=5 |issue=1 |pages=16802 |doi=10.1038/srep16802 |pmc=4652161|doi-access=free}}</ref><ref name="SemNM2020">{{cite journal |last1=Sorace |first1=Anna G. |last2=Elkassem |first2=Asser A. |last3=Galgano |first3=Samuel J. |last4=Lapi |first4=Suzanne E. |last5=Larimer |first5=Benjamin M. |last6=Partridge |first6=Savannah C. |last7=Quarles |first7=C. Chad |last8=Reeves |first8=Kirsten |last9=Napier |first9=Tiara S. |last10=Song |first10=Patrick N. |last11=Yankeelov |first11=Thomas E. |last12=Woodard |first12=Stefanie |last13=Smith |first13=Andrew D. |title=Imaging for Response Assessment in Cancer Clinical Trials |journal=Seminars in Nuclear Medicine |date=November 2020 |volume=50 |issue=6 |pages=488–504 |doi=10.1053/j.semnuclmed.2020.05.001 |pmc=7573201}}</ref>

==Clinical use==

Large scale [[clinical trial]]s 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.<ref>{{cite journal |last1=Zschaeck |first1=Sebastian |last2=Löck |first2=Steffen |last3=Hofheinz |first3=Frank |last4=Zips |first4=Daniel |last5=Saksø Mortensen |first5=Lise |last6=Zöphel |first6=Klaus |last7=Troost |first7=Esther G.C. |last8=Boeke |first8=Simon |last9=Saksø |first9=Mette |last10=Mönnich |first10=David |last11=Seidlitz |first11=Annekatrin |last12=Johansen |first12=Jørgen |last13=Skripcak |first13=Tomas |last14=Gregoire |first14=Vincent |last15=Overgaard |first15=Jens |last16=Baumann |first16=Michael |last17=Krause |first17=Mechthild |title=Individual patient data meta-analysis of FMISO and FAZA hypoxia PET scans from head and neck cancer patients undergoing definitive radio-chemotherapy |journal=Radiotherapy and Oncology |date=August 2020 |volume=149 |pages=189–196 |doi=10.1016/j.radonc.2020.05.022 |pmid=32417350}}</ref> Similar correlations have been found in other cancers, including [[breast cancer]] and [[brain tumour]]s.<ref name="Drake20" /><ref>{{cite journal |last1=Inubushi |first1=Masayuki |last2=Tatsumi |first2=Mitsuaki |last3=Yamamoto |first3=Yuka |last4=Kato |first4=Katsuhiko |last5=Tsujikawa |first5=Tetsuya |last6=Nishii |first6=Ryuichi |title=European research trends in nuclear medicine |journal=Annals of Nuclear Medicine |date=November 2018 |volume=32 |issue=9 |pages=579–582 |doi=10.1007/s12149-018-1303-7 |pmc=6208859|doi-access=free}}</ref> Direct impacts on patient care has not yet been conclusively demonstrated however.<ref name="SemNM2020" />

The use of hypoxia imaging to guide [[radiotherapy]] treatments is an area of active research.<ref>{{cite journal |last1=Lopes |first1=Susana |last2=Ferreira |first2=Sara |last3=Caetano |first3=Marco |title=PET/CT in the Evaluation of Hypoxia for Radiotherapy Planning in Head and Neck Tumors: Systematic Literature Review |journal=Journal of Nuclear Medicine Technology |date=June 2021 |volume=49 |issue=2 |pages=107–113 |doi=10.2967/jnmt.120.249540 |pmid=33361182|doi-access=free}}</ref> 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]].<ref>{{cite journal |last1=Xu |first1=Zuoyu |last2=Li |first2=Xiao-Feng |last3=Zou |first3=Hongyan |last4=Sun |first4=Xilin |last5=Shen |first5=Baozhong |title=18F-Fluoromisonidazole in tumor hypoxia imaging |journal=Oncotarget |date=7 November 2017 |volume=8 |issue=55 |pages=94969–94979 |doi=10.18632/oncotarget.21662 |pmc=5706929|doi-access=free}}</ref><ref>{{cite journal |last1=Marcus |first1=Charles |last2=Subramaniam |first2=Rathan M. |title=Role of Non-FDG-PET/CT in Head and Neck Cancer |journal=Seminars in Nuclear Medicine |date=January 2021 |volume=51 |issue=1 |pages=68–78 |doi=10.1053/j.semnuclmed.2020.07.008}}</ref>

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 (vision)|contrast]] and long injection to imaging delays (due to slow blood clearance) requiring high injected activities.<ref>{{cite journal |last1=Pell |first1=Victoria R. |last2=Baark |first2=Friedrich |last3=Mota |first3=Filipa |last4=Clark |first4=James E. |last5=Southworth |first5=Richard |title=PET Imaging of Cardiac Hypoxia: Hitting Hypoxia Where It Hurts |journal=Current Cardiovascular Imaging Reports |date=March 2018 |volume=11 |issue=3 |pages=7 |doi=10.1007/s12410-018-9447-3 |pmc=5830463|doi-access=free}}</ref>


== References ==
== References ==

Revision as of 16:17, 3 July 2021

[18F]Fluoromisonidazole
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
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC6H818FN3O
Molar mass188.15 g/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]

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, first synthesised in the late 1980s.[3][4][5] It remains among the most popular agents for investigation of hypoxia imaging.[6][7][8]

Mechanism

Chemical changes involved in the reduction and accumulation of FMISO in hypoxic tissue regions
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.{{cite book}}: CS1 maint: location missing publisher (link)
  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.
  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 : official publication, Society 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.
  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.
  8. ^ Kelada, Olivia J.; Carlson, David J. (April 2014). "Molecular Imaging of Tumor Hypoxia with Positron Emission Tomography". Radiation Research. 181 (4): 335–349. doi:10.1667/RR13590.1. PMC 5555673.
  9. ^ a b 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. doi:10.1038/srep16802. PMC 4652161.
  10. ^ a b 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.
  11. ^ a b 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.
  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.
  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.
  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.
  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.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=FMISO&oldid=1031781471"