Radioisotopes in medicine

While it is still early days for targeted radiopharmaceuticals, the slow stream of products that is beginning to reach the market indicates that they have great potential as therapeutic agents that can be designed to act very specifically at any sites, say Sheeja E, Edwin E and Smita G

The consequences of an early realisation of the importance of isotopes and radiation technology and production of radioisotopes had opened the way for applications of isotopes and radiation technology in medicine, industry and agriculture.

Many of the chemical elements have a number of isotopes. The isotopes of an element have the same number of protons in their atoms (atomic number) but different masses due to different numbers of neutrons. In an atom in the neutral state, the number of external electrons also equals the atomic number. These electrons determine the chemistry of the atom. The atomic mass is the sum of the protons and neutrons. There are 82 stable elements and about 275 stable isotopes of these elements.

When a combination of neutrons and protons, which does not already exist in nature, is produced artificially, the atom will be unstable and is called a radioactive isotope or radioisotope. There are also a number of unstable natural isotopes arising from the decay of primordial uranium and thorium. Overall, there are some 1,800 radioisotopes.

At present, there are up to 200 radioisotopes used on a regular basis, and most must be produced artificially.

The use of radioisotopes for diagnosis and therapy of various disease conditions constitutes one of the major applications of isotopes, the world over including India.

These radioisotopes can be swallowed, injected or inhaled. They goes to the specific part of the body to be studied. The nucleus of a radioisotope usually becomes stable by emitting an alpha and/or beta particle (or positron). These particles may be accompanied by the emission of energy in the form of electromagnetic radiation known as gamma rays. This process is known as radioactive decay. These rays can be seen by a special camera and gives the physician an exact idea about the reactions happening in our body.

Radioisotopes can be manufactured in several ways. The most common is by neutron activation in a nuclear reactor. This involves the capture of a neutron by the nucleus of an atom resulting in an excess of neutrons (neutron rich). Some radioisotopes are manufactured in a cyclotron in which protons are introduced to the nucleus resulting in a deficiency of neutrons (proton rich).

Reactor radioisotopes (half-life indicated)

Molybdenum-99 (66 h): Used as the ’parent’ in a generator to produce technetium-99m.

Technetium-99m (6 h): Used in to image the skeleton and heart muscle in particular, but also for brain, thyroid, lungs (perfusion and ventilation), liver, spleen, kidney (structure and filtration rate), gall bladder, bone marrow, salivary and lacrimal glands, heart blood pool, infection and numerous specialised medical studies.

Bismuth-213 (46 min): Used for TAT.

Chromium-51 (28 d): Used to label red blood cells and quantify gastro-intestinal protein loss.

Cobalt-60 (10.5 mth): Formerly used for external beam radiotherapy.

Copper-64 (13 h): Used to study genetic diseases affecting copper metabolism, such as Wilson’s and Menke’s diseases.

Dysprosium-165 (2 h): Used as an aggregated hydroxide for synovectomy treatment of arthritis.

Erbium-169 (9.4 d): Use for relieving arthritis pain in synovial joints.

Holmium-166 (26 h): Being developed for diagnosis and treatment of liver tumours.

Iodine-125 (60 d): Used in cancer brachytherapy (prostate and brain), also diagnostically to evaluate the filtration rate of kidneys and to diagnose deep vein thrombosis in the leg. It is also widely used in radioimmuno-assays to show the presence of hormones in tiny quantities.

Iodine-131 (8 d): Widely used in treating thyroid cancer and in imaging the thyroid; also in diagnosis of abnormal liver function, renal (kidney) blood flow and urinary tract obstruction. A strong gamma emitter, but used for beta therapy.

Iridium-192 (74 d): Supplied in wire form for use as an internal radiotherapy source for cancer treatment (used then removed).

Iron-59 (46 d): Used in studies of iron metabolism in the spleen.

Lutetium-177 (6.7 d): Lu-177 is increasingly important as it emits just enough gamma for imaging while the beta radiation does the therapy on small (eg endocrine) tumours. Its half-life is long enough to allow sophisticated preparation for use.

Palladium-103 (17 d): Used to make brachytherapy permanent implant seeds for early stage prostate cancer.

Phosphorus-32 (14 d): Used in the treatment of polycythemia vera (excess red blood cells). Beta emitter.

Potassium-42 (12 h): Used for the determination of exchangeable potassium in coronary blood flow.

Rhenium-186 (3.8 d): Used for pain relief in bone cancer. Beta emitter with weak gamma for imaging.

Rhenium-188 (17 h): Used to beta irradiate coronary arteries from an angioplasty balloon. Samarium-153 (47 h): Sm-153 is very effective in relieving the pain of secondary cancers lodged in the bone, sold as Quadramet. Also very effective for prostate and breast cancer.

Selenium-75 (120 d): Used in the form of seleno-methionine to study the production of digestive enzymes.

Sodium-24 (15 h): For studies of electrolytes within the body.

Strontium-89 (50 d): Very effective in reducing the pain of prostate and bone cancer. Beta emitter.

Xenon-133 (5 d): Used for pulmonary (lung) ventilation studies.

Ytterbium-169 (32 d): Used for cerebrospinal fluid studies in the brain.

Ytterbium-177 (1.9 h): Progenitor of Lu-177.

Yttrium-90 (64 h): Used for cancer brachytherapy and as silicate colloid for the relieving the pain of arthritis in larger synovial joints. Pure beta emitter.

Radioisotopes of caesium, gold and ruthenium are also used in brachytherapy.

Cyclotron radioisotopes

Carbon-11, Nitrogen-13, Oxygen-15, Fluorine-18: These are positron emitters used in PET for studying brain physiology and pathology, in particular for localising epileptic focus, and in dementia, psychiatry and neuropharmacology studies.

They also have a significant role in cardiology. F-18 in FDG has become very important in detection of cancers and the monitoring of progress in their treatment, using PET.

Cobalt-57 (272 d): Used as a marker to estimate organ size and for in-vitro diagnostic kits.

Gallium-67 (78 h): Used for tumour imaging and localisation of inflammatory lesions (infections).

Indium-111 (2.8 d): Used for specialist diagnostic studies, eg brain studies, infection and colon transit studies.

Iodine-123 (13 h): Increasingly used for diagnosis of thyroid function, it is a gamma emitter without the beta radiation of I-131.

Krypton-81m (13 sec) from Rubidium-81 (4.6 h): Kr-81m gas can yield functional images of pulmonary ventilation, e.g. in asthmatic patients, and for the early diagnosis of lung diseases and function.

Rubidium-82 (65 h): Convenient PET agent in myocardial perfusion imaging.

Strontium-92 (25 d): Used as the `parent’ in a generator to produce Rb-82.

Thallium-201 (73 h): Used for diagnosis of coronary artery disease other heart conditions such as heart muscle death and for location of low-grade lymphomas. The fore going illustrates the level of technology development in the field of isotope processing and applications in the world.

While it is still early days for targeted radiopharmaceuticals, the slow stream of products that is beginning to reach the market indicates that they have great potential as therapeutic agents that can be designed to act very specifically at any sites.

With the increased awareness of the potential of isotope technology, one can safely look forward to increased application, particularly in medicine, radiation chemical processing, food preservation and agriculture.

The writers are with B R Nahata College of Pharmacy, Mandsaur, Madhya Pradesh