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F-18 Radiopharmaceutical

Editor: Dawood Tafti Updated: 2/27/2024 11:03:10 PM

Summary / Explanation

Fluorine-18 (F-18) is a commonly used radionuclide that undergoes positron (beta plus) decay. It is a mainstay in positron emission tomography (PET) imaging. Different molecules (biomarkers) can be labeled with F-18 to form different radiotracers.[1] 

FDA-approved radiotracers are classified as radiopharmaceuticals, each with specific clinical indications. Generally, an F-18 radiopharmaceutical is administered intravenously before a patient obtains a PET/CT scan. The radiopharmaceutical localizes to the target tissue or undergoes a target physiologic process. The PET/CT scanner produces images from the positrons emitted by the radiopharmaceutical. A CT component often acts as a tool for attenuation correction and anatomic localization. The two sets of images (PET data and CT data) are overlayed to analyze the radiotracer distribution with spatial resolution, anatomic correlation, and the ability to quantify uptake.[2]


Many properties of F-18 make it ideal for PET imaging. Most importantly, it undergoes 97% positron decay (3% electron capture).[1] The radioactive F-18 atom emits a positron, a positively charged electron antiparticle, and a neutrino, a massless, noninteractive particle.[3] A positron emitted by F-18 will travel an average length of 1.0 mm in tissue (low linear range) with a mean energy of 250 keV (peak 634 keV) before annihilating on contact with an electron, which is the basis of PET imaging. The low linear range and energy signature allow for excellent spatial resolution when using F-18 radiopharmaceuticals compared to other PET imaging agents.[1][3]

With a half-life of 110 minutes, the biological processes labeled by biomarkers are tracked. This is also a sufficient timeframe for different radiopharmaceuticals to be produced and transported to healthcare facilities without needing an on-site cyclotron. The half-life is short enough that radiation exposure to the public following the injection of a patient with an F-18 radiotracer is negligible after several hours.[1][4] F-18 has minimal effects on the structural or binding properties of the biomarkers to which it is attached.[1] 


F-18 is produced via cyclotron, which involves bombarding a target with protons. There are 2 main ways F-18 is produced in the cyclotron, and the method of choice depends on whether a nucleophilic or electrophilic substitution reaction is required to produce the desired radiopharmaceutical product.[5] Nucleophilic substitution is commonly used to produce F-18 radiopharmaceuticals, with F-18 as the anion.[6] To produce this F-18 anion, enriched water (O-18 H2O) is bombarded with protons. When an electrophilic substitution reaction is needed, O-16 gas is the target of proton bombardment, and radioactive fluorine gas (F-18 F2) is the electrophilic product. One of these F-18 products, the F-18 anion or the F-18 fluorine gas, can be used to create a radiopharmaceutical.[1][7][8][9]

Application Examples

The most common application of F-18 is its linkage to a glucose molecule, in which a hydroxyl group is replaced by the radioactive F-18 atom, yielding F-18-fluorodeoxyglucose (F-18 FDG).[1] Administering F-18 FDG before a whole-body PET/CT enables clinicians to identify hypermetabolic foci of cancer and metastases, as well as other pathology, such as inflammation. Plateau of F-18 FDG accumulation in tissues typically occurs at 20 to 60 minutes. F-18 FDG is typically used to stage and monitor the treatment response of certain cancers.

It can also be used in brain imaging to evaluate dementia. Patients with Alzheimer disease or other forms of dementia will have areas of hypometabolism in the brain, and the distribution of hypometabolism can be a clue to the etiology.[10]

In addition, F-18 FDG is used to evaluate cardiac sarcoidosis, which causes abnormal foci of hypermetabolism in the myocardium due to inflammation.[11] The uptake mechanism in F-18 FDG involves glucose transporters (notably GLUT1). F-18 FDG is transported into cells where hexokinases phosphorylate them. While phosphorylated glucose can be further metabolized, phosphorylated FDG cannot, resulting in trapping and the ability to image tissues with gradually accumulating activity.

Florbetapir and florbetaben are biomarkers that bind to amyloid plaques seen in Alzheimer disease. Labeling 1 of these biomarkers with F-18 and administering it before a PET/CT of the brain helps evaluate for the presence of amyloid plaques and can help rule in or rule out Alzheimer disease.[12][10]

Prostate-specific membrane antigens (PSMA) and fluciclovine can be labeled with F-18 to stage and monitor treatment response in prostate cancer.[13][14] Sodium fluoride (NaF) is a calcium analog with an affinity for hydroxyapatite on the surface of remodeling bone. F-18 NaF can be used to evaluate osseous metastatic disease in prostate cancer.[15] 

F-18 fluorodopa can be used to visualize dopaminergic neurons in the basal ganglia to evaluate Parkinson disease.[1][8] 

F-18 fluoroestradiol can be used in breast cancer imaging.[1][8] 

F-18 flurpiridaz is a radiotracer pending FDA approval for use in myocardial perfusion studies.[16]


F-18 radionuclide is a decay product of oxygen-18 and has a half-life of 110 minutes. Decay mode includes 97% positron emission and 3% electron capture. With a maximal energy of 634 keV and an average photon energy of 250 keV, the mean tissue range of 1.0 (maximum 2.4) allows it to travel a short distance before annihilation. This short distance between the site of emission and the site of annihilation results in excellent resolution characteristics of this radionuclide compared to other positron emitters. When tagged to fluorodeoxyglucose (FDG), F-18 acts as a marker of metabolic activity and has applications in infection evaluation, tumor staging, and cardiac viability. 

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