Wikipedia

Fluoroethyl-L-tyrosine (18F)


Fluoroethyl-l-tyrosine (18F) commonly known as [18F]FET, is a radiopharmaceutical tracer used in positron emission tomography (PET) imaging. This synthetic amino acid, labeled with the radioactive isotope fluorine-18, is a valuable radiopharmaceutical tracer for used in neuro-oncology for diagnosing, planning treatment, and following up on brain tumors such as gliomas. The tracer's ability to provide detailed metabolic imaging of tumors makes it an essential tool in the clinical management of brain cancer patients. Continued advancements in PET imaging technology and the development of more efficient synthesis methods are expected to further enhance the clinical utility of [18F]FET.[2]

Fluoroethyl-L-tyrosine (18F)
Clinical data
Other names18F-FET; O-(2-(18F)fluoroethyl)-l-tyrosine, O-(2-Fluorethyl)-l-thyrosine, l-(18F)FET[1]
Routes of
administration		Intravenous
ATC code
Identifiers
  • O-[2-(18F)Fluoroethyl]-L-tyrosine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H14FNO3
Molar mass227.235 g·mol−1
3D model (JSmol)
  • C1=CC(=CC=C1C[C@@H](C(=O)O)N)OCC[18F]
  • InChI=1S/C11H14FNO3/c12-5-6-16-9-3-1-8(2-4-9)7-10(13)11(14)15/h1-4,10H,5-7,13H2,(H,14,15)/t10-/m0/s1/i12-1
  • Key:QZZYPHBVOQMBAT-LRAGLOQXSA-N

Radiosynthesis

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There are two common pathways for the radiosynthesis of [18F]FET. The first one utilizes a nucleophilic 18F-fluorination of ethyleneglycol-1,2-ditosylate with a subsequent 18F-fluoroethylation of a precursor di-potassium salt of L-tyrosine. This sequence requires two purification steps, two different precursors and two-reactor synthesis module which in not widely available neither in research nor commercial centers. [3][4][5] Schematic for this pathway is presented in Figure 1.[6]

 
Figure 1. Schematic of radiosynthesis using two-step two-pot pathway.

Second route of radiosynthesis is a direct nucleophilic 18F-fluorination a TET (O-(2-tosyloxy-ethyl)-N-trityl-L-tyrosine tertbutylester) pretected precursor followed by acidic hydrolysis of protecting groups. [3][4][7] Schematic for this pathway is presented in Figure 2.[6]

 
Figure 2. Schematic of radiosynthesis using two-step single-pot pathway.

Mechanism of action

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The use of radiolabeled amino acids for brain tumor imaging utilizes the increased proiliferation of tumor cell and overexpression in the amino acid transport system observed in malignant brain tumors. [7][8]

As far as the [18F]FET is concerned following intravenous injection it is transported into cells primarily through amino acid transporters, particularly system L transporters, which are upregulated in many tumor cells . Once inside the cells, [18F]FET does not undergo significant further metabolism but accumulates in tumor tissues, allowing for their visualization and quantification using PET imaging. [8]

The differential uptake provides a high tumor-to-background contrast, facilitating the detection of primary and recurrent brain tumors. Unlike some other PET tracers, [18F]FET does not significantly accumulate in inflammatory tissues, reducing false positives and improving diagnostic specificity. [9][10]

Medical use

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[18F]FET radiotracer has several clinical applications, particularly in neuro-oncology[9][11]:

  • Diagnosis of Brain Tumors - [18F]FET is used to differentiate between malignant and benign brain lesions. It is particularly useful in identifying gliomas, which typically exhibit high [18F]FET uptake.
  • Tumor Grading - intensity of [18F]FET uptake provides insights into the aggressiveness of the tumor. Higher uptake values are often associated with higher tumor grades and more aggressive behavior.
  • Treatment Planning - [18F]FET PET imaging assists in delineating tumor boundaries more accurately than conventional imaging modalities, crucial for planning surgical resection or radiotherapy to ensure maximal tumor removal while sparing healthy tissue.
  • Monitoring Treatment Response - by comparing pre- and post-treatment scans, clinicians can assess the effectiveness of therapeutic interventions. A decrease in [18F]FET uptake post-treatment might indicate a positive response.
  • Detection of Recurrence - [18F]FET is effective in distinguishing between tumor recurrence and post-treatment changes such as radiation necrosis, critical for appropriate clinical management.

Dosimetry

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Recommended activity dose for and adult (weight 70 kg) is in the range of 180 to 250 MBq.

Based on the Radiation Dose to Patients from Radiopharmaceuticals (4th addendum) the absorbed doses in human organs are presented in the table below.[12]

Organ Absorbed dose per unit activity administered [mGy/MBq]
Adults 15 y 10 y 5 y 1 y
Adrenals 0.014 0.017 0.026 0.042 0.077
Bladder 0.085 0.11 0.16 0.22 0.30
Brain 0.013 0.013 0.021 0.034 0.064
Breasts 0.0095 0.012 0.018 0.030 0.057
Gall bladder 0.014 0.017 0.026 0.038 0.068
Stomach 0.015 0.017 0.026 0.039 0.072
Small Intestine 0.020 0.026 0.044 0.071 0.013
Heart 0.013 0.016 0.026 0.039 0.072
Kidneys 0.027 0.033 0.046 0.069 0.12
Liver 0.017 0.022 0.032 0.048 0.088
Lungs 0.014 0.020 0.028 0.042 0.081
Muscle 0.012 0.014 0.023 0.036 0.067
Esophagus 0.012 0.015 0.023 0.036 0.069
Ovaries 0.015 0.018 0.028 0.043 0.077
Pancreas 0.014 0.018 0.027 0.043 0.078
Skin 0.009 0.011 0.18 0.029 0.055
Spleen 0.013 0.016 0.024 0.040 0.073
Testes 0.012 0.016 0.025 0.038 0.070
Thymus 0.012 0.015 0.023 0.036 0.069
Thyroid 0.012 0.015 0.024 0.039 0.073
Uterus 0.017 0.021 0.034 0.051 0.086
Remaining organs 0.012 0.014 0.022 0.035 0.066
Effective dose [mSv/MBq 0.016 0.021 0.031 0.047 0.082

See also

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References

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  1. ^ CID 54255856 from PubChem
  2. ^ Treglia G, Muoio B, Giovanella L (2020). "18F-FET". In Calabria F, Schillaci O (eds.). Radiopharmaceuticals: A Guide to PET/CT and PET/MRI. Cham: Springer International Publishing. pp. 83–88. doi:10.1007/978-3-030-27779-6_4. ISBN 978-3-030-27778-9.
  3. ^ a b Bourdier T, Greguric I, Roselt P, Jackson T, Faragalla J, Katsifis A (July 2011). "Fully automated one-pot radiosynthesis of O-(2-[18F]fluoroethyl)-L-tyrosine on the TracerLab FX(FN) module". Nuclear Medicine and Biology. 38 (5): 645–651. doi:10.1016/j.nucmedbio.2011.01.001. PMID 21718939.
  4. ^ a b Siddiq IS, Atwa ST, Shama SA, Eltaoudy MH, Omar WM (March 2018). "Radiosynthesis and modified quality control of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) for brain tumor imaging". Applied Radiation and Isotopes. 133: 38–44. Bibcode:2018AppRI.133...38S. doi:10.1016/j.apradiso.2017.12.011. PMID 29275040.
  5. ^ Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M, et al. (January 1999). "Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging". Journal of Nuclear Medicine. 40 (1): 205–212. PMID 9935078.
  6. ^ a b Wang M, Glick-Wilson BE, Zheng QH (December 2019). "Facile fully automated radiosynthesis and quality control of O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) for human brain tumor imaging". Applied Radiation and Isotopes. 154: 108852. Bibcode:2019AppRI.15408852W. doi:10.1016/j.apradiso.2019.108852. PMID 31442794.
  7. ^ a b Mueller D, Klette I, Kalb F, Baum RP (July 2011). "Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine based on a cartridge purification method". Nuclear Medicine and Biology. 38 (5): 653–658. doi:10.1016/j.nucmedbio.2011.01.006. PMID 21718940.
  8. ^ a b Muoio B, Giovanella L, Treglia G (2018-09-04). "Recent Developments of 18F-FET PET in Neuro-oncology". Current Medicinal Chemistry. 25 (26): 3061–3073. doi:10.2174/0929867325666171123202644. PMID 29173147.
  9. ^ a b Wang L, Lieberman BP, Ploessl K, Kung HF (January 2014). "Synthesis and evaluation of ¹⁸F labeled FET prodrugs for tumor imaging". Nuclear Medicine and Biology. 41 (1): 58–67. doi:10.1016/j.nucmedbio.2013.09.011. PMC 3895945. PMID 24183614.
  10. ^ Lee TS, Ahn SH, Moon BS, Chun KS, Kang JH, Cheon GJ, et al. (August 2009). "Comparison of 18F-FDG, 18F-FET and 18F-FLT for differentiation between tumor and inflammation in rats". Nuclear Medicine and Biology. 36 (6): 681–686. doi:10.1016/j.nucmedbio.2009.03.009. PMID 19647174.
  11. ^ "Product Characteristic of IASOglio©" (PDF). synektik.com.pl. 28 June 2024. Retrieved 28 June 2024.
  12. ^ Mattsson S, Johansson L, Leide Svegborn S, Liniecki J, Noßke D, Riklund KÅ, et al. (July 2015). "Radiation Dose to Patients from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances" (PDF). Annals of the ICRP. 44 (2 Suppl): 7–321. doi:10.1177/0146645314558019. PMID 26069086.
 

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