Radiopharmaceuticals: medicines that are also radioactive

Most medicines are valued for their chemical effects on the body — blocking a receptor, killing a bacterium, replacing a missing hormone. Radiopharmaceuticals are different: they are valued for the radiation they emit. These are medicines that contain a radioactive atom (a radioisotope) bound to a carrier molecule, and they are used in nuclear medicine for both diagnosing disease and treating it. Because they are radioactive, they behave like no other class of medicine. They decay over time, they require shielded shipping containers, and in some cases they must be used within hours of manufacture. This article explains how they work, how they are handled and regulated, and why their supply chains are unusually fragile.

How radiopharmaceuticals work in diagnosis

Diagnostic radiopharmaceuticals are designed to travel to a specific organ or tissue type, where their radioactivity can be detected from outside the body. The patient receives a small dose — usually by injection — and the emitted radiation is captured by imaging equipment. In PET (positron emission tomography) scans, the radioisotope emits positrons that interact with electrons in the body, producing detectable gamma rays. The most common PET isotope, fluorine-18, is often attached to a glucose analogue called FDG to highlight areas of high metabolic activity such as tumours. In SPECT (single-photon emission computed tomography) scans, the isotope emits gamma rays directly. Technetium-99m is the workhorse of SPECT imaging, used in bone scans, cardiac perfusion studies and kidney function assessments. The chemical carrier determines where the radiopharmaceutical accumulates, while the isotope provides the signal. The radiation dose is generally low and the isotope decays away within hours to days.

Therapeutic radiopharmaceuticals

When the goal is not imaging but the destruction of tissue, higher activities of radiation are used. Therapeutic radiopharmaceuticals deliver radiation directly to diseased cells, reducing exposure to surrounding healthy tissue. The best-established example is iodine-131, which concentrates naturally in thyroid tissue and has been used for decades to treat overactive thyroid conditions and certain thyroid cancers. Iodine-131 has long been included on the WHO Essential Medicines List, reflecting its established role in thyroid disease management worldwide. More recently, targeted radionuclide therapy has emerged, in which a radioactive atom is attached to a molecule — such as a peptide or antibody — that binds to markers on cancer cells. Lutetium-177 and radium-223 are examples of therapeutic isotopes used in this way for specific cancer types. The principle is the same as in diagnosis — a carrier molecule delivers the isotope to the target — but the radiation is strong enough to damage or destroy the cells it reaches.

Handling, transport and regulation

Radiopharmaceuticals sit at the intersection of two regulatory worlds: medicines control and radiation safety. As medicines, they must meet the same standards of quality, safety and efficacy as any other pharmaceutical. Regulators such as SAHPRA in South Africa, the FDA in the United States and the EMA in Europe evaluate them through formal registration processes. As radioactive materials, they are also subject to nuclear regulation, transport restrictions and radiation protection requirements. Shielded containers — typically lead or tungsten — are used for storage and transport. Because every isotope has a physical half-life (the time it takes for half of the radioactivity to decay away), many radiopharmaceuticals have effectively no shelf life. A vial of technetium-99m, with a half-life of about six hours, loses half its activity every six hours. Hospitals must coordinate ordering and use tightly, and staff who prepare and administer these products require specialised training in both pharmacy and radiation safety. Readers in South Africa can search HealthSA to check whether specific radiopharmaceutical products carry SAHPRA registration.

Isotope supply chains and fragility

The production of medical radioisotopes is one of the most concentrated supply chains in all of medicine. Most diagnostic technetium-99m is derived from molybdenum-99, which is produced in a handful of research reactors around the world — including South Africa's SAFARI-1 reactor at Pelindaba. When any one of these reactors requires scheduled maintenance or experiences an unplanned shutdown, global supply can drop sharply, causing imaging delays. PET isotopes such as fluorine-18, with a half-life of just under two hours, cannot be shipped long distances at all. They require a cyclotron within a few hours' drive of the hospital, compounding the logistics. Therapeutic isotopes such as lutetium-177 and actinium-225 face their own supply constraints, as production capacity is limited and the number of qualified suppliers is small. This fragility means that radiopharmaceutical supply is not just a question of manufacturing capacity, but of geography, physics and timing — a challenge unlike any other in the medicine supply chain.