RADIOPHARMACY Diagnostic Nuclear Medicine 3 continue 6

Nuclear medicine is a branch of medical imaging that uses small amounts of radioactive material to diagnose and determine the severity of or treat a variety of diseases, including many types of cancers, heart disease, gastrointestinal, endocrine, neurological disorders and other abnormalities within the body. Because nuclear medicine procedures are able to pinpoint molecular activity within the body, they offer the potential to identify disease in its earliest stages as well as a patient’s immediate response to therapeutic interventions..

Cardiac nuclear medicine is useful in diagnosing coronary artery disease and cardiomyopathy and identifying possible damage to the heart from chemotherapy or radiotherapy. Nuclear medicine, or radionuclide, diagnostic imaging procedures are non-invasive and, with the exception of intravenous injections, are usually painless medical tests that help physicians diagnose and evaluate medical conditions. These imaging scans use radioactive materials called radiopharmaceuticals or radiotracers

CARDIAC IMAGING Perfusion agents for cardiac imaging. Radiopharmaceuticals are useful in cardiac imaging as agents that provide information on the regional myocardial blood perfusion. They typically are administered as part of a cardiac stress test so as to provide information at peak cardiac output. The patient will run on a treadmill to “stress” the heart. IV coronary vessel dilating agents are used in place of the treadmill when the patient is not physically able to exercise. Examples of these pharmacological agents are dipyridamole, adenosine, and dobutamine. The patient will also be imaged when the heart is at rest, usually 3 hrs following stress study.

1. Thallous chloride Thallium-201 (Tl-201 ) It is used for myocardial perfusion imaging in the diagnosis of coronary artery disease and localization of myocardial infarction. Bio-distribution (1) Tl-201 is a monovalent cation with distribution analogous to a potassium ion (K ) ; myocardial uptake is by active transport via the Na /K adenosine Triphosphatase (ATPase) pump. (2) Bio-distribution is generally proportional to organ blood flow at the time of injection, with blood clearance by myocardium, kidneys, and liver. (3) Tl-201 is excreted slowly. (4) Redistribution allowing to perform rest study in 3 hrs following stress study with single injection given once at peak stress. Physical half -life: 73 hr Primary radiation emissions: Kev (mean peak 73 keV) γ- rays Administration and dosage. IV, 3 mCi (111 MBq)

2.Tc-99m sestamibi ( Tc99m MIBI) exists as a sterile, pyrogen-free IV injection after kit reconstitution with Tc-99m pertechnetate and heating at 100°C for 10 min. Bio-distribution (1) Tc-99m sestamibi is a cation complex that has been found to accumulate in viable myocardium by passive diffusion into the myocyte with subsequent binding to the mitochondria within the cell. (2) The major pathway for clearance (excretion) of Tc-99m sestamibi is the hepatobiliary system with bile. (3) Tow injections are needed for stress and rest studies, given with each study. Administration and dosage. IV, 10 mCi (370 MBq) Stress study 20 mCi (740 MBq) Rest study

3. Tc-99m tetrofosmin exists as a sterile and pyrogen- free IV injection ready for labelling with Tc-99m pertechnetate. Tc-99m tetrofosmin is a lipophilic, cationic complex that has been found to accumulate in viable myocardium. After the Tc-99m pertechnetate is added to the kit, it must be heated in a hot water bath at 100°C for 10 min to form Tc-99m MAG3. Bio-distribution The major pathways for clearance of Tc-99m tetrofosmin are the hepatobiliary system and the renal system. Administration and dosage. IV, same as MIBI.

Myocardial Infarction

Myocardial Ischemia

THYROID IMAGING Overview The basic function of the thyroid gland is the product ion of thyroid hormone for the regulation of metabolism. The thyroid hormones are produced within the gland through the organification of iodine obtained from the oxidation of available iodide circulating in the blood.

The function of the thyroid gland can be evaluated by the uptake of I-131 or I-123, allowing the detection of hypothyroidism with decreased uptake and hyperthyroidism with increased uptake. The inability of the body to distinguish between the isotopes of iodine provides a perfect metabolic tracer for the thyroid biochemical system.

Thyroid scan An image taken of a patient's thyroid gland after the patient swallows radioactive iodine or IV injection of technetium. The image shows the thyroid gland in action as it accumulates radioactive material. Thyroid scanning is used to determine how active thyroid tissue is in manufacturing thyroid hormone. This can help the physician to determine whether inflammation of the thyroid gland (thyroiditis) is present. It can also show the presence and degree of overactivity of the gland (hyperthyroidism).

Thyroid scanning is especially helpful in evaluating thyroid nodules, particularly after a fine-needle aspiration biopsy has failed to provide a diagnosis. A scan can reveal whether a thyroid nodule is functioning. A functioning nodule actively takes up iodine to produce thyroid hormone, and so it produces a localized 'hot' area on the image. A non-functioning nodule does not take up iodine, and it produces a localized 'cold' area. Most nodules, particularly if they are functioning, are not malignant.

1.Sodium iodide iodine-123 ( I-123 ) is a radiopharmaceutical available in either solution or capsule form for oral administration. Bio-distribution (1)Orally administered iodine is rapidly absorbed from the Gastrointestinal (GI ) tract ; thyroid gland uptake is evident within minutes. (2) Sodium iodide I-123 is considered an ideal radiopharmaceutical for iodine uptake and imaging studies because of its short half- life and useful 160 keV primary gamma (γ) emissions. Physical half -life: 13 hr Primary radiation emissions: 160 keV.27 γ energy photons Administration and dosage. Oral : 100 μCi (0.1 mCi or 3.7 MBq)

2. Sodium iodide iodine-131 ( I-131 ) Is not considered an ideal radioiodine radiopharmaceutical for iodine uptake and imaging studies because of its long half- life, poor imaging properties, and the high radiation dose to the thyroid from its β decay component. The radiation dose from the high-energy β particle with the imaging potential of its γ emissions make this radionuclide the agent of choice for therapeutic treatment of hyperthyroidism and thyroid cancer. Physical half life: 8 days Decay mode: by β decay Primary gamma emissions: 360 keV γ energy photons. Administration and dosage. I-131 is available as either a capsule or in solution for oral administration. 100 μCi (0.1 mCi or 3.7 MBq)

Tc-99m pertechnetate is a monovalent anion with an ionic radius similar to iodide. As a result, the pertechnetate ion is trapped by the thyroid gland in a fashion similar to iodide. The two species (iodide and pertechnetate) are different in that Tc-99m pertechnetate is not organified or incorporated into thyroid hormone, and it is subsequently released unchanged. Tc-99m pertechnetate Thyroid Uptake and Scan As I-123 is not always available, and I-131 is not an ideal diagnostic agent, Tc-99m pertechnetate is the most commonly radiopharmaceutical to evaluate the function of the thyroid gland. Administration and dosage. IV, 5mCi (185 MBq)

Tc-99m sodium pertechnetate (NaTc-99m O4-)

Normal Thyroid

Cold Nodule

Hot Nodule

The chemical form of 99mTc available from the Moly generator is sodium pertechnetate (NaTc-99m O4-). The pertechnetate ion, Tc-99m O4, having the oxidation state 7+ for 99mTc, resembles the permanganate ion. It has a configuration of a pyramidal tetrahedron with Tc+ located at the centre and four oxygen atoms at the apex and corners of the pyramid. Chemically, 99mTcO4 is a rather nonreactive species and does not label any compound by direct addition. In 99mTc-labeling of many compounds, prior reduction of Tc-99m from the 7+ state to a lower oxidation state is required. Various reducing agents are used, among these, stannous chloride (SnCl2 2H2O), is the most commonly used reducing agent in most preparations of Tc-99m labelled compounds Tc-99m pertechnetate

Clinical application 1-Thyroid scintigraphy Determination of thyroid uptake and morphology Diagnosis and localization of hot/cold nodules 2-Salivary gland scintigraphy To assess salivary gland function and duct status 3-Imaging of gastric mucosa To diagnose ectopic gastric mucosa (Meikles diverticulum) 4-Lachrymal gland scintigraphy To evaluate nasolachriml drainage 5-Testicular imaging

Tc-99m pertechnetate Clinical application 6-Barin scintigraphy Visualization of brain lesions when blood brain barrier is defect (BBB) 7-In vivo labeling of RBCs Regional blood pool imaging Detection of GIT bleeding 8- Labeling most of the pharmaceuticals used in NM studies

Thank you and Good Luck Prof. Dr. Omar Shebl Zahra