Fluorine-18

Last updated
Fluorine-18, 18F
Fluorine-18 decay.svg
Decay over 24 hours
General
Symbol 18F
Names fluorine-18, 18F, F-18,
Fluorine-18
Protons (Z)9
Neutrons (N)9
Nuclide data
Natural abundance Radioisotope
Half-life (t1/2)109.771(20)  min
Isotope mass 18.0009380(6) Da
Spin 1+
Excess energy 873.431±0.593 keV
Binding energy 137369.199±0.593 keV
Decay products 18O
Decay modes
Decay mode Decay energy (MeV)
Positron emission (97%)0.6335
Electron capture (3%)1.6555
Isotopes of fluorine
Complete table of nuclides

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.

Contents

Natural occurrence

18
F
is a natural trace radioisotope produced by cosmic ray spallation of atmospheric argon as well as by reaction of protons with natural oxygen: 18O + p → 18F + n. [1]

Synthesis

In the radiopharmaceutical industry, fluorine-18 is made using either a cyclotron or linear particle accelerator to bombard a target, usually of natural or enriched [18O]water [2] with high energy protons (typically ~18 MeV). The fluorine produced is in the form of a water solution of [18F]fluoride, which is then used in a rapid chemical synthesis of various radio pharmaceuticals. The organic oxygen-18 pharmaceutical molecule is not made before the production of the radiopharmaceutical, as high energy protons destroy such molecules (radiolysis). Radiopharmaceuticals using fluorine must therefore be synthesized after the fluorine-18 has been produced.

History

First published synthesis and report of properties of fluorine-18 were in 1937 by Arthur H. Snell, produced by the nuclear reaction of 20Ne(d,α)18F in the cyclotron laboratories of Ernest O. Lawrence. [3]

Chemistry

Fluorine-18 is often substituted for a hydroxyl group (–OH) in a radiotracer parent molecule, due to similar steric and electrostatic properties. This may however be problematic in certain applications due to possible changes in the molecule polarity.

Applications

Fluorine-18 is one of the early tracers used in positron emission tomography (PET), having been in use since the 1960s. [4] Its significance is due to both its short half-life and the emission of positrons when decaying. A major medical use of fluorine-18 is: in positron emission tomography (PET) to image the brain and heart; to image the thyroid gland; as a radiotracer to image bones and seeking cancers that have metastasized from other locations in the body and in radiation therapy treating internal tumors.

Tracers include sodium fluoride which can be useful for skeletal imaging as it displays high and rapid bone uptake accompanied by very rapid blood clearance, which results in a high bone-to-background ratio in a short time [5] and fluorodeoxyglucose (FDG), where the 18F substitutes a hydroxyl. New dioxaborolane chemistry enables radioactive fluoride (18F) labeling of antibodies, which allows for positron emission tomography (PET) imaging of cancer. [6] A Human-Derived, Genetic, Positron-emitting and Fluorescent (HD-GPF) reporter system uses a human protein, PSMA and non-immunogenic, and a small molecule that is positron-emitting (18F) and fluorescent for dual modality PET and fluorescence imaging of genome modified cells, e.g. cancer, CRISPR/Cas9, or CAR T-cells, in an entire mouse. [7] The dual-modality small molecule targeting PSMA was tested in humans and found the location of primary and metastatic prostate cancer, fluorescence-guided removal of cancer, and detects single cancer cells in tissue margins. [8]

Related Research Articles

<span class="mw-page-title-main">Positron emission tomography</span> Medical imaging technique

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.

<span class="mw-page-title-main">Bone scintigraphy</span> Nuclear medicine imaging technique

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).

Fluorodeoxyglucose (<sup>18</sup>F) Chemical compound

[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.

<span class="mw-page-title-main">Molecular imaging</span> Imaging molecules within living patients

Molecular imaging is a field of medical imaging that focuses on imaging molecules of medical interest within living patients. This is in contrast to conventional methods for obtaining molecular information from preserved tissue samples, such as histology. Molecules of interest may be either ones produced naturally by the body, or synthetic molecules produced in a laboratory and injected into a patient by a doctor. The most common example of molecular imaging used clinically today is to inject a contrast agent into a patient's bloodstream and to use an imaging modality to track its movement in the body. Molecular imaging originated from the field of radiology from a need to better understand fundamental molecular processes inside organisms in a noninvasive manner.

Oxygen-18 is a natural, stable isotope of oxygen and one of the environmental isotopes.

<span class="mw-page-title-main">Glutamate carboxypeptidase II</span> Enzyme

Glutamate carboxypeptidase II (GCPII), also known as N-acetyl-L-aspartyl-L-glutamate peptidase I, NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the FOLH1 gene. Human GCPII contains 750 amino acids and weighs approximately 84 kDa.

Preclinical imaging is the visualization of living animals for research purposes, such as drug development. Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or molecular level, in animals responding to physiological or environmental changes. Imaging modalities that are non-invasive and in vivo have become especially important to study animal models longitudinally. Broadly speaking, these imaging systems can be categorized into primarily morphological/anatomical and primarily molecular imaging techniques. Techniques such as high-frequency micro-ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) are usually used for anatomical imaging, while optical imaging, positron emission tomography (PET), and single photon emission computed tomography (SPECT) are usually used for molecular visualizations.

Emission computed tomography (ECT) is a type of tomography involving radioactive or emissions. Types include positron emission tomography (PET) and Single-photon emission computed tomography (SPECT).

<span class="mw-page-title-main">Brain positron emission tomography</span> Form of positron emission tomography

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.

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.

<span class="mw-page-title-main">Desmethoxyfallypride</span> Chemical compound

Desmethoxyfallypride is a moderate affinity dopamine D2 receptor/D3 receptor antagonist used in medical research, usually in the form of the radiopharmaceutical [F-18]-desmethoxyfallypride (DMFP(18F)) which has been used in human studies as a positron emission tomography (PET) radiotracer.

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.

<span class="mw-page-title-main">FMISO</span> Chemical compound

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.

<span class="mw-page-title-main">Dihydrotetrabenazine</span> Chemical compound

Dihydrotetrabenazine or DTBZ is an organic compound with the chemical formula C19H29NO3. It is a close analog of tetrabenazine. DTBZ and its derivatives, when labeled with positron emitting isotopes such as carbon-11 and fluorine-18, are used as PET radioligands for examining VMAT2.

<span class="mw-page-title-main">PET radiotracer</span> Radioligand used for diagnostic purposes

PET radiotracer is a type of radioligand that is used for the diagnostic purposes via positron emission tomography imaging technique.

A PSMA scan is a nuclear medicine imaging technique used in the diagnosis and staging of prostate cancer. It is carried out by injection of a radiopharmaceutical with a positron or gamma emitting radionuclide and a prostate-specific membrane antigen (PSMA) targeting ligand. After injection, imaging of positron emitters such as gallium-68 (68Ga), copper-64 (64Cu), and fluorine-18 (18F) is carried out with a positron emission tomography (PET) scanner. For gamma emitters such as technetium-99m (99mTc) and indium-111 (111In) single-photon emission computed tomography (SPECT) imaging is performed with a gamma camera.

<span class="mw-page-title-main">Peter J. H. Scott</span>

Peter J. H. Scott FRSC CChem is a British and American chemist and radiochemist who is a professor of radiology, professor of pharmacology and professor of medicinal chemistry, as well as a core member of the Rogel Cancer Center at the University of Michigan in the United States. He is Chief of Nuclear Medicine and director of the University of Michigan Positron Emission Tomography (PET) Center, and runs a research group developing new radiochemistry methodology and novel PET radiotracers.

Arterial input function (AIF), also known as a plasma input function, refers to the concentration of tracer in blood-plasma in an artery measured over time. The oldest record on PubMed shows that AIF was used by Harvey et al. in 1962 to measure the exchange of materials between red blood cells and blood plasma, and by other researchers in 1983 for positron emission tomography (PET) studies. Nowadays, kinetic analysis is performed in various medical imaging techniques, which requires an AIF as one of the inputs to the mathematical model, for example, in dynamic PET imaging, or perfusion CT, or dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).

Gallium (<sup>68</sup>Ga) gozetotide Radiopharmaceutical medication

Gallium (68Ga) gozetotide or Gallium (68Ga) PSMA-11 sold under the brand name Illuccix among others, is a radiopharmaceutical made of 68Ga conjugated to prostate-specific membrane antigen (PSMA) targeting ligand, Glu-Urea-Lys(Ahx)-HBED-CC, used for imaging prostate cancer by positron emission tomography (PET). The PSMA targeting ligand specifically directs the radiolabeled imaging agent towards the prostate cancerous lesions in men.

References

  1. SCOPE 50 - Radioecology after Chernobyl Archived 2014-05-13 at the Wayback Machine , the Scientific Committee on Problems of the Environment (SCOPE), 1993. See table 1.9 in Section 1.4.5.2.
  2. Fowler J. S. and Wolf A. P. (1982). The synthesis of carbon-11, fluorine-18 and nitrogen-13 labeled radiotracers for biomedical applications. Nucl. Sci. Ser. Natl Acad. Sci. Natl Res. Council Monogr. 1982.
  3. Anonymous (1937-01-15). #5 shows the abstract of Arthur H. Snell about the discovery of the first produced fluorine-18. "Minutes of the Pasadena Meeting, December 18 and 19, 1936". Physical Review. 51 (2): 142–150. Bibcode:1937PhRv...51..142.. doi:10.1103/PhysRev.51.142. ISSN   0031-899X.
  4. Blau, Monte; Ganatra, Ramanik; Bender, Merrill A. (January 1972). "18F-fluoride for bone imaging". Seminars in Nuclear Medicine. 2 (1): 31–37. doi:10.1016/S0001-2998(72)80005-9. PMID   5059349.
  5. Ordonez, A. A.; DeMarco, V. P.; Klunk, M. H.; Pokkali, S.; Jain, S.K. (October 2015). "Imaging Chronic Tuberculous Lesions Using Sodium [18F]Fluoride Positron Emission Tomography in Mice". Molecular Imaging and Biology. 17 (5): 609–614. doi:10.1007/s11307-015-0836-6. PMC   4561601 . PMID   25750032.
  6. Rodriguez, Erik A.; Wang, Ye; Crisp, Jessica L.; Vera, David R.; Tsien, Roger Y.; Ting, Richard (2016-04-27). "New Dioxaborolane Chemistry Enables [18F]-Positron-Emitting, Fluorescent [18F]-Multimodality Biomolecule Generation from the Solid Phase". Bioconjugate Chemistry. 27 (5): 1390–1399. doi:10.1021/acs.bioconjchem.6b00164. PMC   4916912 . PMID   27064381.
  7. Guo, Hua; Harikrishna, Kommidi; Vedvyas, Yogindra; McCloskey, Jaclyn E; Zhang, Weiqi; Chen, Nandi; Nurili, Fuad; Wu, Amy P; Sayman, Haluk B. (2019-05-23). "A fluorescent, [ 18 F]-positron-emitting agent for imaging PMSA allows genetic reporting in adoptively-transferred, genetically-modified cells". ACS Chemical Biology. 14 (7): 1449–1459. doi:10.1021/acschembio.9b00160. ISSN   1554-8929. PMC   6775626 . PMID   31120734.
  8. Aras, Omer; Demirdag, Cetin; Kommidi, Harikrishna; Guo, Hua; Pavlova, Ina; Aygun, Aslan; Karayel, Emre; Pehlivanoglu, Hüseyin; Yeyin, Nami; Kyprianou, Natasha; Chen, Nandi (March 2021). "Small Molecule, Multimodal [18F]-PET and Fluorescence Imaging Agent Targeting Prostate Specific Membrane Antigen: First-in-Human Study". Clinical Genitourinary Cancer. 19 (5): 405–416. doi: 10.1016/j.clgc.2021.03.011 . PMC   8449790 . PMID   33879400.
Lighter:
fluorine-17
Fluorine-18 is an
isotope of fluorine
Heavier:
fluorine-19
Decay product of:
neon-18
Decay chain
of fluorine-18
Decays to:
oxygen-18