Fluorine-18 (¹⁸F) is a

fluorine Fluorine is a chemical element with the symbol F and atomic number 9. It is the lightest halogen and exists at standard conditions as a highly toxic, pale yellow diatomic gas. As the most electronegative reactive element, it is extremely reactiv ...

radioisotope A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferr ...

which is an important source of

positron The positron or antielectron is the antiparticle or the antimatter counterpart of the electron. It has an electric charge of +1 '' e'', a spin of 1/2 (the same as the electron), and the same mass as an electron. When a positron collide ...

s. It has a mass of 18.0009380(6) u and its

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...

is 109.771(20) minutes. It decays by positron emission 96% of the time and

electron capture Electron capture (K-electron capture, also K-capture, or L-electron capture, L-capture) is a process in which the proton-rich nucleus of an electrically neutral atom absorbs an inner atomic electron, usually from the K or L electron shells. ...

4% of the time. Both modes of decay yield stable oxygen-18.

Natural occurrence

is a natural trace radioisotope produced by

cosmic ray spallation Cosmic ray spallation, also known as the x-process, is a set of naturally occurring nuclear reactions causing nucleosynthesis; it refers to the formation of chemical elements from the impact of cosmic rays on an object. Cosmic rays are highly ener ...

of atmospheric argon as well as by reaction of protons with natural oxygen: ¹⁸O + p → ¹⁸F + n.SCOPE 50 - Radioecology after Chernobyl
, the Scientific Committee on Problems of the Environment (SCOPE), 1993. See table 1.9 in Section 1.4.5.2.

Synthesis

In the radiopharmaceutical industry, fluorine-18 is made using either a

cyclotron A cyclotron is a type of particle accelerator invented by Ernest O. Lawrence in 1929–1930 at the University of California, Berkeley, and patented in 1932. Lawrence, Ernest O. ''Method and apparatus for the acceleration of ions'', filed: Jan ...

or linear particle accelerator to bombard a target, usually of natural or enriched sup>18Oater with high energy

protons A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron m ...

(typically ~18 MeV). The fluorine produced is in the form of a water solution of sup>18F luoride, 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 Radiolysis is the dissociation of molecules by ionizing radiation. It is the cleavage of one or several chemical bonds resulting from exposure to high-energy flux. The radiation in this context is associated with ionizing radiation; radiolysis is ...

). 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 Ernest Orlando Lawrence (August 8, 1901 – August 27, 1958) was an American nuclear physicist and winner of the Nobel Prize in Physics in 1939 for his invention of the cyclotron. He is known for his work on uranium-isotope separation fo ...

Chemistry

Fluorine-18 is often substituted for a

hydroxyl group In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

in a radiotracer parent molecule, due to similar

steric Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

and

electrostatic Electrostatics is a branch of physics that studies electric charges at rest ( static electricity). Since classical times, it has been known that some materials, such as amber, attract lightweight particles after rubbing. The Greek word for ...

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 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, ...

(PET), having been in use since the 1960s. 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, looking for 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 and fluorodeoxyglucose (FDG), where the ¹⁸F substitutes a

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...

. New dioxaborolane chemistry enables radioactive fluoride (¹⁸F) labeling of

antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...

, which allows for

(PET) imaging of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

. 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.

CRISPR/Cas9 Cas9 (CRISPR associated protein 9, formerly called Cas5, Csn1, or Csx12) is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic ...

, or CAR T-cells, in an entire mouse. The dual-modality small molecule targeting PSMA was tested in humans and found the location of primary and metastatic

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that su ...

, fluorescence-guided removal of cancer, and detects single cancer cells in tissue margins.

References

{{Isotope, element=fluorine , lighter= fluorine-17 , heavier= fluorine-19 , before=

neon-18 Neon (10Ne) possesses three stable isotopes: , , and . In addition, 17 radioactive isotopes have been discovered, ranging from to , all short-lived. The longest-lived is with a half-life of . All others are under a minute, most under a second. ...

, after= oxygen-18 Isotopes of fluorine Radiopharmaceuticals Medicinal radiochemistry Positron emitters