![]() | |
Clinical data | |
---|---|
Other names | 18F-FET; O-(2-(18F)fluoroethyl)-l-tyrosine, O-(2-Fluorethyl)-l-thyrosine, l-(18F)FET [1] |
Routes of administration | Intravenous |
ATC code | |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
CompTox Dashboard (EPA) | |
Chemical and physical data | |
Formula | C11H14FNO3 |
Molar mass | 227.235 g·mol−1 |
3D model (JSmol) | |
| |
|
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]
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]
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]
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]
Animal studies in rodents have demonstrated high uptake of [18F]FET in brain tumors, with a significant tumor-to-brain ratio, making it a useful tracer for brain tumor imaging. [11]
Heiss et al. conducted in vitro and in vivo investigation of transport mechanism and uptake of [18F]FET. The experimented utilized human colon carcinoma cells (SW 707) and xenotransplanted, tumor-bearing mice. [18F]FET was shown to be transported mainly (>80%) by the l-type amino acid transporter system, which was inhibited by 2-amino-2-norbornanecarboxylic acid (BCH) and not incorporated into proteins in SW 707 cells. This study also help to establish the half-life of [18F]FET in the plasma (94 min), brain-to-blood ratio (0.86) and shower statistically significant higher uptake of [18F]FET in the xenotransplanted tumor than in any other organ beside the pancreas. [12]
In 1999 biodistribution studies in mice with colon carcinoma cells were conducted by Wester et al. The study showed a high uptake of radioactivity in the pancreas (18% injected dose (ID)/g) at 60 min after injection of [18F]FET. [13] The brain (2.17% ID/g) and the tumors (6.37% ID/g) showed moderate uptakes of the radiotracer. Rapid distribution of [18F]FET with completion time of less than 5 min was observed for liver, kidney and blood. The other organs showed little elevated uptake with time. [18F]FET remained intact in the tissue tested samples (pancreas, brain, tumor and plasma) and no incorporation of radiotracer into proteins was observed. [13]
Another biodistribution study was carried out by Wang et al. In this study the comparison between [18F]FDG and [18F]FET in rats with gliomas showed a moderate uptake and a long retention time of [18F]FET in liver, kidneys, lung, heart and blood whereas a diminished uptake was observed in healthy brain. The maximum uptake of [18F]FET and [18F]FDG in the glioma was observed at 60 min post injection 1.49% and 2.77% ID/g, respectively. The tumor-to-brain ratios were 3.15 for [18F]FET and 1.44 for [18F]FDG. PET images of [18F]FET showed higher uptake and better contrast for tumor vs health tissue. [14]
Biodistribution studies in mice and rats have shown that [18F]FET is retained in tumor tissues and exhibits low uptake in inflammatory tissues, enhancing its specificity for tumor imaging. [15] In vivo experiments have also indicated that [18F]FET can effectively differentiate between high-grade and low-grade tumors based on the level of tracer uptake. [14] . Additionally, longitudinal studies in animal models have shown that [18F]FET PET imaging can be used to monitor tumor progression and response to therapy, providing valuable insights into the efficacy of treatment regimens. [16] These preclinical findings have laid the groundwork for the successful translation of [18F]FET PET imaging into clinical practice.
[18F]FET radiotracer has several clinical applications, particularly in neuro-oncology [9] [17] :
Initial [18F]FET dosimetry was estimated by Pauleit et al. based on human dynamic PET scans after injection of 400 MBq of radiotracer at 70 and 200 min. [18] The highest dose was received by bladder (0.060 mGy/MBq) and subsequently by kidneys (0.020 mGy/MBq) and uterus (0.022 mGy/MBq). No increased uptake was observed in the liver, bone, intestine, lung, heart, or pancreas. The effective dose determined by human study was 0.0165 mSv/MBq whereas the effective dose based on biodistribution data of mice was estimated to be 0.009 mSv/MBq. [18] [19]
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. [20]
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 |
[18F]FET has a relatively short shelf life which is a result of radioactive isotope fluorine-18 half life (109.8 minutes). However, in comparison to radiotracers labelled with carbon-11 isotope, it still allows for radiotracer to be distributed through land and air up to 6 hour delivery radius.
Currently [18F]FET is comercially available in Europe as IASOglio© in France (MA number 34009 550 105 1 7/34009 550 105 2 4) and in Poland (MA number 27420). The Marketing Authorization Holder is radiopharmaceutical company called Curium™. [21]
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, regional chemical composition, and absorption. Different tracers are used for various imaging purposes, depending on the target process within the body.
Nuclear medicine, or nucleology, is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging is, in a sense, radiology done inside out, because it records radiation emitted from within the body rather than radiation that is transmitted through the body from external sources like X-ray generators. In addition, nuclear medicine scans differ from radiology, as the emphasis is not on imaging anatomy, but on the function. For such reason, it is called a physiological imaging modality. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) scans are the two most common imaging modalities in nuclear medicine.
A bone scan or bone scintigraphy is a nuclear medicine imaging technique of the bone. It can help diagnose a number of bone conditions, including cancer of the bone or metastasis, location of bone inflammation and fractures, and bone infection (osteomyelitis).
[18F]Fluorodeoxyglucose (INN), or fluorodeoxyglucose F 18, also commonly called fluorodeoxyglucose and abbreviated [18F]FDG, 2-[18F]FDG or FDG, is a radiopharmaceutical, specifically a radiotracer, used in the medical imaging modality positron emission tomography (PET). Chemically, it is 2-deoxy-2-[18F]fluoro-D-glucose, a glucose analog, with the positron-emitting radionuclide fluorine-18 substituted for the normal hydroxyl group at the C-2 position in the glucose molecule.
Fluorine-18 (18F) is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380(6) u and its half-life is 109.771(20) minutes. It decays by positron emission 96.7% of the time and electron capture 3.3% of the time. Both modes of decay yield stable oxygen-18.
EF5 is a nitroimidazole derivative used in oncology research. Due to its similarity in chemical structure to etanidazole, EF5 binds in cells displaying hypoxia.
2-Fluoroethanol is the organic compound with the formula CH2FCH2OH. This colorless liquid is one of the simplest stable fluorinated alcohols. It was once used as a pesticide. The related difluoro- and trifluoroethanols are far less dangerous.
The standardized uptake value (SUV) is a nuclear medicine term, used in positron emission tomography (PET) as well as in modern calibrated single photon emission tomography (SPECT) imaging for a semiquantitative analysis. Its use is particularly common in the analysis of [18F]fluorodeoxyglucose ([18F]FDG) images of cancer patients. It can also be used with other PET agents especially when no arterial input function is available for more detailed pharmacokinetic modeling. Otherwise measures like the fractional uptake rate (FUR) or parameters from more advanced pharmacokinetic modeling may be preferable.
Brain positron emission tomography is a form of positron emission tomography (PET) that is used to measure brain metabolism and the distribution of exogenous radiolabeled chemical agents throughout the brain. PET measures emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream. The emission data from brain PET are computer-processed to produce multi-dimensional images of the distribution of the chemicals throughout the brain.
Mefway is a serotonin 5-HT1A receptor antagonist used in medical research, usually in the form of mefway (18F) as a positron emission tomography (PET) radiotracer.
Radiofluorination is the process by which a radioactive isotope of fluorine is attached to a molecule and is preferably performed by nucleophilic substitution using nitro or halogens as leaving groups. Fluorine-18 is the most common isotope used for this procedure. This is due to its 97% positron emission and relatively long 109.8 min half-life. The half-life allows for a long enough time to be incorporated into the molecule and be used without causing exceedingly harmful effects. This process has many applications especially with the use of positron emission tomography (PET) as the aforementioned low positron energy is able to yield a high resolution in PET imaging.
Florbetaben, sold under the brand name Neuraceq, is a diagnostic radiotracer developed for routine clinical application to visualize β-amyloid plaques in the brain. It is a fluorine-18 (18F)-labeled stilbene derivative.
Metabolic trapping refers to a localization mechanism of synthesized radiocompounds in the human body. It can be defined as the intracellular accumulation of a radioactive tracer based on the relative metabolic activity of the body's tissues. It is a basic principle of the design of radiopharmaceuticals as metabolic probes for functional studies or tumor location.
Fluorodeoxyglycosylamine is a product of fluorodeoxyglucose and biological amines. The Maillard reaction of sugars and amines results in the formation of glycosylamines and Amadori products that are of biological significance, for drug delivery, role in central nervous system, and other potential applications.
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.
Fluciclovine (18F), also known as anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid, and sold under the brand name Axumin, is a diagnostic agent used for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated prostate specific antigen (PSA) levels.
Philip F. Cohen is a Canadian clinical director of Nuclear Medicine working out of the Lions Gate Hospital in North Vancouver, British Columbia. As a nuclear medicine physician, he is a pioneer in the usage of 3-D imaging techniques to improve diagnosis of bone disease and injury in collaboration with the Medical Imaging Research Group at University of British Columbia. Furthermore, Cohen has been involved in clinical research trials of new radiopharmaceuticals. To that effect, Cohen was the first recipient of a research grant from the Lions Gate Hospital Foundation, one of several peer-reviewed awards that would follow.
Carbon-11 choline is the basis of medical imaging technologies. Because of its involvement in biologic processes, choline is related to diseases, leading to the development of medical imaging techniques to monitor its concentration. When radiolabeled with 11CH3, choline is a useful a tracer in PET imaging. Carbon-11 is radioactive with a half-life of 20.38 minutes. By monitoring the gamma radiation resulting from the decay of carbon-11, the uptake, distribution, and retention of carbon-11 choline can be monitored.
Positron emission tomography for bone imaging, as an in vivo tracer technique, allows the measurement of the regional concentration of radioactivity proportional to the image pixel values averaged over a region of interest (ROI) in bones. Positron emission tomography is a functional imaging technique that uses [18F]NaF radiotracer to visualise and quantify regional bone metabolism and blood flow. [18F]NaF has been used for imaging bones for the last 60 years. This article focuses on the pharmacokinetics of [18F]NaF in bones, and various semi-quantitative and quantitative methods for quantifying regional bone metabolism using [18F]NaF PET images.
Neil Vasdev is a Canadian and American radiochemist and expert in nuclear medicine and molecular imaging, particularly in the application of PET. Radiotracers developed by the Vasdev Lab are in preclinical use worldwide, and many have been translated for first-in-human neuroimaging studies. He is the director and chief radiochemist of the Brain Health Imaging Centre and director of the Azrieli Centre for Neuro-Radiochemistry at the Centre for Addiction and Mental Health (CAMH). He is the Tier 1 Canada Research Chair in Radiochemistry and Nuclear Medicine, the endowed Azrieli Chair in Brain and Behaviour and Professor of Psychiatry at the University of Toronto. Vasdev has been featured on Global News, CTV, CNN, New York Times, Toronto Star and the Globe and Mail for his innovative research program.