What is a PET Drug?
PET drugs are used in diagnostic PET imaging studies to assess disease states based on biochemical pathways in the human body. “Biochemical imaging” is different from other forms of imaging like MRI or CT scans, which measure anatomic changes in the body (e.g., the formation of a tumor). Since biochemical changes proceed anatomic changes resulting from disease, PET imaging can lead to earlier detection when compared to other forms of imaging.
The active ingredient in a PET drug contains an unstable radioactive atom that undergoes decay by positron emission. The positron-emitting atom is chemically bound to a molecular framework that is specific for the intended diagnostic study for the PET drug. For example, Fludeoxyglucose F 18 Injection, or FDG, has an active ingredient consisting of an unstable F-18 atom bound to a glucose framework. Since the molecular structure of FDG is similar to ordinary glucose, FDG is used in PET imaging to detect diseases that result from altered rates of glucose metabolism in the body. Since many different diseases alter glucose metabolism, FDG is the most common PET drug used in the US.
The chemical properties of positron-emitting atoms (also known as radionuclides due to their radioactive decay) allow the synthesis of a wide variety of biochemically-active molecules for use in PET imaging. As of mid-2021, 16 PET drugs had been approved by the FDA for diagnostic studies ranging from cardiology, neurology, and oncology.
The half-lives of the most common radionuclides for PET drugs are very short. For example, the half-life of F-18 is 109.8 minutes. The half-life is the time for a radioactive sample to decay by one-half of its original amount. Thus, approximately one-half of the FDG active ingredient is lost every two hours. The short half-life translates into very short shelf lives for PET drugs, which means that PET drugs must be used at or very near the point of manufacture. During radioactive decay, the radiation emitted by PET radionuclides has an energy of 511 keV, which lies in the gamma ray region of the electromagnetic spectrum. This value is significantly higher that the energy of the radiation emitted by traditional radioactive drugs used in diagnostic nuclear medicine. For example, Tc-99m based radioactive drugs emit radiation with an energy of about 141 keV. This means that PET drugs must be shielded more extensively to prevent excessive radiation exposure to personnel. Together, the short half-lives and high energy emissions of PET drugs define the safety profile of PET drugs and practice standards for manufacturing, handling, and distribution. These topics are discussed throughout this website.
Most radionuclides for PET drugs are produced by proton bombardment of stable nuclei with a particle accelerator. For example, F-18 is produced by proton bombardment of O‑18 nuclei. This requires the location of a cyclotron at the PET drug manufacturing facility. Recently, generator-produced radionuclides for PET drugs have become available. For example, generator-produced Ga-68 (half-life = 67.7 min) is available for the manufacturing of FDA-approved PET drugs. This opens the door to the preparation of PET drugs at facilities that don’t have a cyclotron.
Although the synthesis of each PET drug varies from one to the next, the manufacturing of FDG serves as the prototypical workflow for F-18 based PET drugs. The full details of this process are beyond the scope of this description, but the key manufacturing steps may be summarized as follows:
Radionuclide production by cyclotron bombardment
Radiochemical synthesis
Membrane filter sterilization and final product formulation
Product sampling and quality control testing
