Radiopharmaceuticals are drug products that contain a biological moiety and a radioactive element. The biological construct targets a physiological or pathophysiological process of interest, allowing the localization of radiation that in turn may be imaged or used to affect therapy. Most radiopharmaceuticals are used in diagnostic medical imaging. They are also used in therapeutic applications, such as in treatment of hyperthyroidism, thyroid cancer, polycythemia and alleviation of bone pain.
The patient-oriented service that embodies the scientific knowledge and professional judgement required to improve and promote health the safe and efficacious use of radioactive drugs for diagnosis and therapy is called nuclear pharmacy.
Properties
Radiopharmaceuticals lack pharmacological effects because the mass quantities range from picogram (pg) to nanogram (ng) per kilogram (kg) of administered dose. Most radiopharmaceuticals are prepared as sterile, pyrogen free intravenous solutions or suspensions to be administered directly to the patient. Other routes of administration include intradermal, oral, interstitial and inhalation (e.g., radioactive gases, aerosols).The radioactive component of a radiopharmaceutical is referred to as a radionuclide. Nuclides are identified as atoms having a specific number of protons and neutrons in the nucleus. A nuclide is typically identified by the chemical symbol of the element with a mass number to the upper left superscript indicating the sum of protons and neutrons (e.g., iodide131 is indicated 131I). When the atom is radioactive, it is called a radionuclide. Radionuclides undergo spontaneous radioactive decay accompanied by the release of energy. The distribution, metabolism, and elimination of the radiopharmaceutical can be determined by measuring the energy with imaging equipment. There are four major types of radiations emitted through this process: alpha, beta, gamma and X-rays. Alpha and beta radiations are not useful in medical imaging and are therefore undesirable in diagnostic applications. Most diagnostic radiopharmaceuticals use penetrating gamma radiation, which can be easily detected and converted into imaging data.
Quality control
Generally the term "radioactivity" is used to describe the phenomenon of radioactive decay and to express the physical quantity of this phenomenon. The radioactivity of a preparation is the number of nuclear disintegrations or transformations per unit time. Absolute radioactivity measurement requires a specialised lab but identification and measurement of radiation can be carried out relatively by comparing with standardised preparations provided by the labs recognised by component authorities.
Applications
Following are the applications of radiopharmaceuticals in diagnosis: Cardiovascular imaging; Skeletal imaging; Lung imaging; Hepatic imaging; Renal imaging; Thyroid imaging; Brain imaging; Breast imaging; Deep vein thrombosis imaging and tumours imaging.
Perfusion agents for cardiac imagin - Radiopharmaceuticals are useful in cardiac imaging as agents that provide information on the regional myocardial perfusion. They typically are administered as part of a cardiac stress so as to provide information at peak cardiac output. Examples of perfusion agents are Thallous chloride Tl-201 (201Tl), Technetium Tc-99m sestamibi (Tc-MIBI), Technetium Tc-99m Tetrofosmin, Rubidium chloride Rb-82 (82Rb), Ammonia N-13. Agents used to measure cardiac function (regional myocardial wall motion) are Technetium Tc-99m-labelled red blood cells (Tc-RBCs), Pyrophosphate injection USP, and Technetium Tc-99m albumin (99mTc-HSA) injection. Agents for imaging myocardial infraction are pyrophosphate injection USP and phosphates USP.
Skeletal imaging agents - 99mTc-labelled bone agents are useful in the detection of bone lesions that are associated with metastatic neoplasms, metabolic disorders, and infections of the bone. The imaging advantage of 99mTc, coupled with the sensitivity of bone agent localization in skeletal bone hydroxyapatite, allows for detection of bone pathology before evidence in shown by conventional X-rays. Bone marrow imaging agents - Images that localize in the bone marrow are useful in the evaluation of pathologies that affect bone marrow.
Radiopharmaceuticals are used to evaluate both pulmonary perfusion and pulmonary ventilation, to detect pulmonary embolism and to access pulmonary function before pneumonectomy. Pulmonary perfusion imaging agents - Technetium Tc-99m albumin aggregated (99mTc-MAA). Pulmonary ventilation imaging agents - Radioactive gases, which can provide valuable information about regional lung investigation. Radiopharmaceuticals that are used are either radioactive gases or radioaerosols. E.g. Xenon Xe-133 (133Xe), Xenon Xe-127 (127Xe), Krypton Kr-88m (88mKr), Radioaerosols.
Hepatic imaging requires the use of two different classes of radiopharmaceuticals to evaluate the two cell types responsible for hepatic function. Reticuloendothelial system imaging - The liver, spleen and bone marrow are evaluated with radiolabelled colloidal material, ranging in size from 0.1-0.3 µm. These particles are rapidly cleared from the blood by phagocytosis by the kuppfer cells or trapped in the space Disse that is found between the polygonal hepatocytes and the kuppfer cells. - e.g. Technetium Tc-99m sulphur colloid (Tc2S7). Hepatobiliary imaging agents - Hepatobiliary imaging agents include Iminodiacetic acid (IDA) derivatives for their lipophillicity that allows them to selectively cleared by carrier-mediated hepatocyte metabolic pathways, Cholecystokinetic agents are used to empty the gallbladder in the fasting patients prior to injection of IDA compounds and other agents used are Technetium Tc-99m disofenin (99mTc-DISIDA), Technetium Tc-99m lidofenin (99mTc-HIDA) and Technetium Tc-99m mebrofenin.
The use of radiopharmaceuticals to determine renal function or renal morphology is based on the two physiological mechanisms responsible for excretion: glomerular filtration and tubular secretion. Agents cleared by glomerular filtration - These are used in determination of GFR, renal artery perfusion and visualization of the collecting system. Technetium Tc-99m pentetate (99mTc-DTPA) and sodium iothalamate I-125 injection. Tubular secretion agents - These are used to evaluate renal tubular function and measure effectiveness renal plasma flow. E.g. Iodohippurate I-131 hippuran, Technetium Tc-99m mertiatide (99mTc-MAG3). Renal cortical imaging agents - These are used to evaluate renal anatomy because of their ability to accumulate in the kidney and provide anatomical imaging data. E.g. Technetium Tc-99m Gluceptate (99mTc-GLH) and Technetium Tc-99m succimer (99mTc-DMSA).
The function of the thyroid gland can be evaluated by the uptake of 131I or 123I, allowing the detection of hypothyroidism with decreased uptake and hyperthyroidism with increased uptake. E.g. Sodium Iodide I-131 (131I), Sodium Iodide I-123 (123I) and 201Tl (parathyroid imaging).
Cerebral perfusion brain-imaging agents - Radiopharmaceuticals for evaluating brain perfusion, the regional uptake of these agents is directly proportional to the cerebral blood flow. Used in the diagnosis of an altered regional blood perfusion in stroke. E.g.Technetium Tc-99m exametazime (99mTc-HMPAO) and Technetium Tc-99m bicisate (99mTc-ECD). Carrier-mediated transport mechanisms - 18F fludeoxyglucose aid in the valuation of cerebral function by mapping the distribution of glucose metabolism. Cerebrospinal fluid (CSF) dynamics - Indium In-111pentetate (111In) is useful in the evaluation of hydrocephalus and in detecting CSF leaks.
Technetium Tc-99m sestamibi (Tc-MIBI) is used for breast imaging as a second line of evaluating breast lesions in patients with an abnormal mammogram or a palpable breast mass.
Technetium Tc-99m apcitite (99mTc apcitite) is used to image acute venous thrombosis in the lower extremities of patients who have the signs and symptoms of acute venous thrombosis.
The usefulness of radiopharmaceuticals in the detection of tumours varies in sensitivity and specificity, with differences in tumour location and type. E.g. Gallium citrate Ga-67(67Ga), Indium In-111 pentetreotide, Iobenguane I-131 injection (131I-MIBG), Thallous chloride T1-201, Fludeoxyglucose F-18 USP and Technetium Tc-99m depreotide.
Conclusion
Radiopharmaceuticals play a crucial role in the diagnosis of the major complicated diseases. Most of the radiopharmaceuticals are directly injected into blood stream as IV injections; problems with the formulation of radiopharmaceuticals can result in altered distribution patterns. Quality control programmes should identify such problems before patient administration to avoid any troubles coupled with the use of radiopharmaceuticals as diagnostic agents. The regulated use of radiopharmaceuticals may solve so many problems associated with the diagnosis of many diseases.
(The author is with SRIPMS, Coimbatore)