**4. Radiopharmaceuticals**

The first radioactive tracer experiment was performed by George Charles de Hevesy in the 1920s. In the 1930s, Irene Curie and Frederic Joliot discovered artificial radioactivity. The discovery of the cyclotron by Ernest Lawrence opened the door for the production of radio‐ tracers of practically every element, thus enabling investigators to design radiotracers for the study of specific biochemical processes.

The European Pharmacopoeia describes "radiopharmaceutical" as any medical product which, when ready to use, contains one or more radionuclides included for a medicinal purpose [11].

Although the field of Nuclear Medicine evolved into a more sophisticated molecular‐imaging technology, the term "radiopharmaceuticals" has extended to novel radiolabeled molecular‐ imaging probes [1, 4].

Most radiopharmaceuticals consist of a combination of a radioactive molecule—a radionuclide —and a biologically active molecule or a drug that acts as a carrier and determines localization and biodistribution. For a few radionuclides (such as radioiodine, gallium, or thallium), the radioactive atoms themselves act as the radiopharmaceuticals [3].

The radionuclide emits radiation that is detected externally using gamma cameras or PET cameras. Certain characteristics are desirable for clinically useful radiopharmaceuticals. Radionuclide decay should result in emissions of suitable energy (100–200 keV is ideal for gamma cameras) and in sufficient abundance for external detection. Particulate radiation (e.g., beta emissions) increases the patient radiation dose, and should be reserved for therapeutic use. Effective half‐life should be only long enough for the intended application (usually a few hours). The radionuclide should be carrier‐free—that is, not contaminated by other stable radionuclides or other radionuclides of the same element. Technetium‐99m most closely fulfills these features for the gamma camera, and fluorine‐18 for PET [2, 3].

Once a decision about a suitable nuclide has been made, an appropriate agent must be selected to carry the isotope. There are many different radiopharmaceuticals available to study the different parts of the body, which can be administered by injection, ingestion, or even inhala‐ tion. They are administered in sub‐pharmacological doses (<100 µg) and "trace" a particular physiological or pathological process in the body, portraying the physiology, biochemistry, or pathology, without affecting it or without causing any other physiological effect [2, 3]. Thus, with the exception of some tracers in radio‐immunoscintigraphy and radiotherapy, hypersen‐ sitivity reactions against tracers are very rare, as the administered quantities are below a threshold to trigger immune response. Even in known hypersensitivity to iodinated substances (i.e., hypersensitivity against contrast media in radiology), iodine tracers can be safely used for diagnosis and therapy [1].

Understanding the mechanism and rationale for the use of each agent is critical to under‐ standing the normal and pathological findings demonstrated scintigraphically.
