This course covers various kinds of radiopharmaceuticals, calculating effective half life, determining radiochemical purity, and applications of radiopharmaceuticals used in medical science.

Radiopharmaceuticals (RP) are chemical substances that contain radioactive atoms within their structure. They are used as tracers in nuclear medicine technology for diagnostic and therapeutic purposes.

More than 95% of radiopharmaceuticals are used for diagnostic purposes. They have following (shown below) ideal characteristics :

  • primary photon energy between 50-500KeV,
  • suitable physical half-life, low toxicity, and
  • suitable chemical form and reactivity.

Structurally, a radiopharmaceutical (Figure 1) is a combination of a radionuclide (α, β, or γ emitter) and a ligand (proteins, peptides, drug or an antibiotic)

99mTc (Radionuclide) + Ciprofloxacin (Ligand) = 99mTc-Ciprofloxacin (Radiopharmaceutical)

Figure 1. A radiopharmaceutical
Figure 1. A Radiopharmaceutical

Among various available radionuclides, I-131, In-111, and Tc-99m are the most promising. They have following characteristics as mentioned below.

  • suitable physiochemical properties
  • emission characteristics
  • easy availability
  • short half-life
  • preferential localization into desired organs, and
  • cost effectiveness

Nearly 80% of all radiopharmaceutical used in nuclear medicine are 99mTc labeled compounds.

Since they are intended for patients, they undergo quality control test. Quality control tests include physicochemical and biological tests. These tests are unique to radiopharmaceuticals, and are not applicable to conventional drugs.

  1. The physicochemical tests (in vitro) include testing
  • physical appearance
  • pH
  • ionic strength
  • radionuclidic purity
  • radiochemical purity (by ITLC), precipitation, chromatography, electrophoresis, and distillation
  • radioassay
  • chemical purity

B. The biological tests include sterility and pyrogenicity testing (LAL test).

Effective Half-life

A radionuclide decays with a definite half-life called physical half-life that is denoted by Tp or t1/2. Radiopharmaceuticals have a biologic half-life (time needed for RP to disappear in biologic system) denoted by Tb. Effective half-life is the sum of physical and biological rate constants. So,

                              λe = λp + λb

Since, λ = 0.693/t1/2,

Radiochemical purity

Radiochemical purity of a radiopharmaceutical is the fraction of total radioactivity in a desired chemical form. Radiochemical impurities in radiopharmaceuticals arise from decomposition due to the action of solvent, change in pH and temperature of reaction mixture, radiolysis (depends upon half-life, and energy emitted by the radionuclide), or presence of oxidizing and reducing agents. Stabilizers such as ascorbic acid, sodium ascorbate, or sodium sulfite are added to enhance the stability of the radiopharmaceutical.

Radiochemical purity of radiopharmaceutical is determined by instant thin layer chromatography (ITLC).

Three species exist in a vial containing 99mTc-labeled preparation i.e. radiocomplexed drug, free radionuclide and R/H products of the radionuclide. ITLC method is used in order to estimate the amount of three components, hence the labeling yield. ITLC-SA & ITLC-SG paper strips are used as stationary phase and appropriate mobile phases are used to measure labeling efficiency.

Protocol for the determination of Radiochemical Purity of 99mTc-INH

Applications of Radiopharmaceuticals  

Radiopharmaceuticals are being used in nuclear medicine since the 1950s. To produce radiopharmaceuticals, radioisotopes with short half-lives are preferred to minimize the radiation dose  and risk of prolonged exposure in patients. The use of radiopharmaceuticals for imaging organ function and disease indicate their unique capability in nuclear medicine.

Unlike other imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography (US), nuclear medicine procedures can detect physiological as well as biological functions, and metabolic activities of the organ being studied and provides more specific information about the organ function and dysfunction.

Over 100 radiopharmaceuticals in use today. Most are used to diagnose various diseases, but for some diseases they can help in therapy. Radiopharmaceuticals used in therapy are labeled with beta emitting radionuclides. These are used for management of thyroid cancers, bone pain palliation, improvement in quality of life of cancer patients, and treatment of joint pain in rheumatoid arthritis. Microprocessor-controlled automated synthesis modules have been developed for rapid and reliable synthesis of PET radiopharmaceuticals.