**5.1. Diagnosis**

**4. Radiopharmaceuticals**

162 Advanced Technology for Delivering Therapeutics

purpose [11].

imaging probes [1, 4].

for diagnosis and therapy [1].

study of specific biochemical processes.

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

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

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

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

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

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

Understanding the mechanism and rationale for the use of each agent is critical to under‐

standing the normal and pathological findings demonstrated scintigraphically.

radioactive atoms themselves act as the radiopharmaceuticals [3].

these features for the gamma camera, and fluorine‐18 for PET [2, 3].

Nuclear Medicine dedicates primarily to the diagnosis of medical conditions. Depending on the type of examination, radiopharmaceuticals are administered in the most suitable way, for example, intravenously or orally. Afterwards, external detectors capture the radiation emitted by those radiopharmaceuticals and images are formed, showing the radiopharmaceutical uptake distribution and, subsequently, the targeted sites.

## **5.2. Targeted therapy**

Drugs are designed to treat diseases, correcting abnormal cellular or molecular processes [4]. In theory, any highly specific imaging tracer can be used for therapy if labeled with the suitable radionuclide.

The term theranostics refers to substances that have both diagnostic and therapeutic roles. One classic example is radioiodine, used to diagnose and treat some thyroid pathologies. Thera‐ nostics has played a vital role in radiation‐based therapies, especially when using targeted radiopharmaceuticals [9, 12].

Therapeutic procedures in Nuclear Medicine use high‐dose, nonpenetrating radiation emitting, targeted radiopharmaceuticals. Most therapies use beta‐emitters (I‐131, Y‐90, and Lu‐ 177), but Auger‐, Alpha‐, or conversion electron emitters are also good candidates [3, 8]. The targeting ligands can also be radiolabeled with suitable positron emitters such as F‐18 and Ga‐ 68, for PET monitoring and evaluation purposes [9].

Theranostics agents play a major role in the development of radiopharmaceuticals, validating its target profile and early‐disease diagnostics. They help choose the more adequate candidates and therefore are frequently used by the pharmaceutical industry [9].
