THALLIUM CHLORIDE (201TI) :THALLIUM CHLORIDE (201TI) Presented by Mathew Variamattom


Objectives :Objectives Discuss the Clinical application of 201TI Describe the Nuclear Medicine procedures Explain the indications Discuss the contraindications Explain the Patient Preparations Describe the Patient History Describe the Patient Information


Objectives cont’d :Objectives cont’d Discuss the precautions Explain the method of Localization Discuss the method of Administration Discuss the method of acquisition Explain the method of processing Discuss the normal and abnormal results Discuss the interpretation


Clinical Applications of 201TI :Clinical Applications of 201TI Brand Name: Thallium Generic Name: Thallous Chloride 201Tl Purpose: For Diagnostic Use Energies: 68-80 keV k x-ray, 135, 167 keV Tl 201 Injection is supplied in isotonic solution as a sterile, non- pyrogenic diagnostic radiopharmaceutical for intravenous administration.


Clinical Applications of 201TI cont’d :Clinical Applications of 201TI cont’d The aqueous solution at the time of calibration contains 2mCi/ml Tl 201. It is made isotonic with 9mg/ml sodium chloride and is preserved with 9mg/ml benzyl alcohol. The pH is adjusted with hydrochloric acid and/or sodium hydroxide solution.


Clinical Applications of 201TI cont’d :Clinical Applications of 201TI cont’d Thallium Tl 201 is cyclotron produced with no carrier added and contains no less than 98% Thallium Tl 201. It is recommended that Tl 201 Injection be administered close to calibration time to minimize the effect of higher levels of radionuclide contaminants pre-and post calibration. The concentration of each radionuclide contaminant changes with time.


Procedures :Procedures For patients undergoing resting thallium studies, imaging is optimally begun within 10-20 minutes after injection. Several investigators have reported improved myocardial-to-background ratios when patients are injected in the fasting state, in an upright posture, or after briefly ambulating. The upright position reduces the hepatic and gastric Thallium Tl 201 concentration.


Procedures cont’d :Procedures cont’d Best results with thallium imaging performed in conjunction with exercise stress testing appear to be obtained if the thallium is administered when the patient reaches maximum stress and when the stress is continued for 30 seconds to one minute after injection. Imaging should begin within ten minutes post-injection since target-to-background ratio is optimum by that time.


Procedures cont’d :Procedures cont’d There is significant decreases in the target-to-background ratios of lesions attributable to transient ischemia by two hours after the completion of stress imaging. For the localization of parathyroid hyperactivity, Thallous Chloride Tl 201 Injection may be administered before, with or after a minimal dose of a thyroid imaging agent such as sodium pertechnetate Tc99m or sodium iodide l 123 to enable thyroid subtraction imaging.


Procedures cont’d :Procedures cont’d 201TI is a monovalent cationic metal used in cardiac imaging. It is obtained from a 201Pb – 201TI generator. Thallium Tl 201, with a physical half-life of 73.1 hours, decays by electron capture to mercury Hg 201 with gamma emissions between 140 and 179 keV. The lower energy X-rays obtained from the Mercury Hg 201 daughter of Tl 201 are recommended for myocardial imaging.


Procedures cont’d :Procedures cont’d Because the mean percent disintegration at 68.9 to 80.3 keV is much greater than the combination of gamma-4 and gamma-6 mean percent disintegration. Photons that are useful for detection and imaging are gamma 4 and gamma 8 rays. A number of pharmacological stress inducers are available for use with 201TI. Dipyridamole (Persantine) is a coronary vasodilator that has been employed in 201TI cardiac imaging.


Patient preparations :Patient preparations Identify the patient Verify doctor’s order Explain the procedure Instruct patient to be NPO for 4-12 hours (no sugar, caffeine, dairy products) Patient should be well rested and avoid strenuous exercise the day of test before exam.


Patient History :Patient History Do you have a history or family history of cancer? If so what type and for how long? Do you have a history or family history of parathyroid disease? Do you have a history or family history of thyroid disease? Have you had recent thyroid or parathyroid surgery? Have you had head and neck radiation therapy? What medications are you taking? Females: Are you pregnant or nursing?


INDICATIONS :INDICATIONS Thallous Chloride Tl 201 Injection is useful in myocardial perfusion imaging using either planar or SPECT (Single Photon Computed Tomography) techniques for the diagnosis and localization of myocardial infarction. It also have prognostic value regarding survival, when used in the clinically stable patient following the onset of symptoms of an acute myocardial infarction, to assess the site and size of the perfusion defect.


INDICATIONS cont’d :INDICATIONS cont’d Tl 201 Injection may also be useful in conjunction with exercise stress testing as an adjunct in the diagnosis of ischemic heart disease (atherosclerotic coronary artery disease). It is usually not possible to differentiate recent from old myocardial infarction, or to differentiate between recent myocardial infarction and ischemia. Thallous Chloride Tl 201 Injection is indicated also for the localization of sites of para-thyroid hyperactivity in patients with elevated serum calcium and parathyroid hormone levels.


INDICATIONS cont’d :INDICATIONS cont’d It may also be useful in pre-operative screening to localize extra thyroidal and mediastinal sites of the parathyroid hyperactivity and for post-surgical reexamination. Thallous Chloride Tl 201 Injection has not been adequately demonstrated to be effective for the localization of normal parathyroid glands.


CONTRAINDICATIONS :CONTRAINDICATIONS Following the administration of Thallous Chloride Tl 201 Injection, adverse anaphyl-actoid reactions have been reported (characterized by cardiovascular, respiratory, and cutaneous symptoms), some severe enough to require treatment. Hypotension, pruritus, flushing and diffuse rash which responds to antihistamines have been reported. Other reported events include itching, nausea/vomiting, mild diarrhea, tremor, shortness of breath, chills, fever, conjunctivitis, sweating and blurred vision.


DOSAGE :DOSAGE The recommended adult dose of intravenous Thallous Chloride Tl 201 Injection for planar myocardial imaging is 1-2 mCi. The recommended intravenous doses for SPECT myocardial imaging are 2-3 mCi. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration.


Method of Localization :Method of Localization Localization: similar to potassium, distributes with Na/K pump within 20 minutes of injection, then seeps out of myocardium and redistributes. Tb = 10 days +- 2.5 days


Method of Administration :Method of Administration Thallium Chloride Tl 201 Injection is supplied in an isotonic solution as a sterile, non-pyrogenic diagnostic radiopharmaceutical for intravenous administration. Following absorption, thallium uptake into the circulatory system is rapid. Thallium is quickly distributed from the blood to the tissues.


Method of Administration cont’d :Method of Administration cont’d Each milliliter contains 1 millicurie Thallium Chloride Tl 201 at calibration time, made isotonic with 9 milligrams sodium chloride and preserved with 0.9% (v/v) benzyl alcohol. It is recommended that Thallium Chloride Tl 201 Injection be administered close to calibration time to minimize the effect of higher levels of radionuclide contaminants during pre-and post-calibration. The concentration of each radionuclide contaminant changes with time.


Preparation and Handling Procedures for Tl 201 Injection :Preparation and Handling Procedures for Tl 201 Injection Store at controlled room temperature 20° to 25°C (68° to 77°F). Waterproof gloves should be worn during the handling and injection period. Adequate shielding during the life of the radioactive drug should be maintained by using the lead shield and cover and by using a syringe shield for withdrawing and injecting Thallous Chloride Tl 201 Injection.


Risk Factors :Risk Factors Exposure to high levels of thallium can result in harmful health effects. A study on workers exposed on the job over several years reported nervous system effects, such as numbness of fingers and toes, from breathing thallium.


Drug Interactions and Precautions :Drug Interactions and Precautions No Drug Interactions listed. studying patients in whom myocardial infarction or ischemia is known or suspected, care should be taken to assure continuous clinical monitoring and treatment in accordance with safe, accepted procedure. Exercise stress testing should be performed only under the supervision of a qualified physician and in a laboratory equipped with appropriate resuscitation and support apparatus.


Drug Interactions and Precautions cont’d :Drug Interactions and Precautions cont’d Data are not available concerning the effect of marked alterations in blood glucose, insulin, or pH (such as is found in diabetes mellitus) on the quality of Thallous Chloride Tl 201 Injection scans. Attention is directed to the fact that thallium is a potassium analog, and since the transport of potassium is affected by these factors, the possibility exists that the thallium may likewise be affected.


Drug Interactions and Precautions cont’d :Drug Interactions and Precautions cont’d For the localization of parathyroid hyperactivity, Thallous Chloride Tl 201 may be administered before, with or after a minimal dose of a thyroid imaging agent such as sodium pertechnetate Tc 99m or sodium iodide I123 to enable thyroid subtraction imaging. Do not use after the expiration time and date (5 days maximum after calibration time) stated on the label. Do not use if contents are turbid.


Drug Interactions and Precautions cont’d :Drug Interactions and Precautions cont’d The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration. Thallous Chloride Tl 201 Injection, as all radioactive materials, must be handled with care and used with appropriate safety measures to minimize external radiation exposure to clinical personnel. Care should also be taken to minimize radiation exposure to patients in a manner consistent with proper patient management.


Drug Interactions and Precautions cont’d :Drug Interactions and Precautions cont’d Thallous Chloride Tl 201 Injection should not be given to a pregnant woman except when benefits clearly outweigh the potential risks. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, nursing should not be undertaken when a patient is administered radioactive material.


Drug Interactions and Precautions cont’d :Drug Interactions and Precautions cont’d Safety and effectiveness in the pediatric population has not been established. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.


CLINICAL PHARMACOLOGY :CLINICAL PHARMACOLOGY Thallous Chloride Tl 201 Injection with no carrier added has been found to accumulate in viable myocardium in a manner analogous to that of potassium. Experiments in human volunteers using labeled microspheres have shown that the myocardial distribution of Thallous Chloride Tl 201 Injection correlates well with regional perfusion.


CLINICAL PHARMACOLOGY cont’d :CLINICAL PHARMACOLOGY cont’d In clinical studies, thallium images have been found to visualize areas of infarction as "cold" or nonlabeled regions which are confirmed by electrocardiographic and enzyme changes. When the "cold" or nonlabeled regions comprise a substantial portion of the left ventricle, the prognosis for survival is unfavorable.


CLINICAL PHARMACOLOGY cont’d :CLINICAL PHARMACOLOGY cont’d Regions of transient myocardial ischemia corresponding to areas perfused by coronary arteries with partial stenoses have been visualized when Thallous Chloride Tl 201 Injection was administered in conjunction with an exercise stress test. Body habitus may interfere with visualization of the inferior wall.


Method of Localization :Method of Localization After intravenous administration, Thallous Chloride Tl 201 Injection clears rapidly from the blood with maximal concentration by normal myocardium occurring at about ten minutes. It will, in addition, localize in parathyroid adenomas; it is not specific since it will localize to a lesser extent in sites of para-thyroid hyperplasia and other abnormal tissues such as thyroid adenoma, neoplasia (e.g., parathyroid carcinoma) and sarcoid.


Method of Localization cont’d :Method of Localization cont’d Biodistribution is generally proportional to organ blood flow at the time of injection. Blood clearance of Thallous Chloride Tl 201 Injection is primarily by the myocardium, kidneys, thyroid, liver and stomach with the remainder distributing fairly uniformly throughout the body.


Method of Localization cont’d :Method of Localization cont’d The dosimetry data reflect this distribution pattern and are based on a biological half-life of 11 days and an effective half-life of 2.4 days. Thallous Chloride Tl 201 Injection is excreted slowly and to an equal extent in both feces and urine. This technique has limited sensitivity for detecting para-thyroid adenomas smaller than 5mm in diameter.


Image Acquisition :Image Acquisition Imaging should begin 10 minutes after the administration of 2-4 mCi of 201TI. Mercury x-rays in the 68-80 keV range are emitted during the decay of 201TI. A 30% window is centered over 72 keV. The use of a second 20% window centered on the 167 keV gamma ray emissions is optional.


Image Acquisition cont’d :Image Acquisition cont’d Use a LEAP or a high resolution collimator Matrix size of 64 x 64 or 128 x 128 word mode. A minimum of 600,000 counts in the total field of view or 8 minutes of acquisition time is necessary to obtain high quality images.


Images :Images


Images cont’d :Images cont’d


Image Processing :Image Processing Myocardial perfusion data are evaluated by viewing the images to detect zones of diminished tracer localization and by quantification of the relative regional distribution of the agent. SPECT images are usually quantified by stacking the reconstructed/reoriented short slices onto a bull’s eye display, where the apex is at the center and the basal slice is at the periphery.


Image Processing cont’d :Image Processing cont’d The individual short and long axis images are reviewed for homogeneity of tracer localization. The image sets should then ideally be displayed adjacent to one another and adjusted to optimize matching slices.


Interpretations :Interpretations Normal results: Heterogeneous uptake of the left ventricular myocardium Heterogeneous uptake of the right ventricular myocardium Abnormal results: Areas of little or no uptake exhibiting a cold spot. If the lack of uptake matches the stress results in the same area, it may be infarcted myocardium or severe ischemic tissue. Defect on both scans - infarction


Conclusion :Conclusion Thallium Chloride TI201 acts as a potassium analogue in the body. It is taken up into the myocardial tissue both actively by sodium/potassium cellular pump and also passively along an electrochemical gradient. Thallium is an excellent marker of myocardial perfusion. It also rapidly redistributes, reaching an equilibrium at 3-4 hours.


Questions/Answers :Questions/Answers Question 1 What are the energies of 201TI?


Slide 45:Ans. 1 Energies: 68-80 keV k x-ray, 135, 167 keV


Question 2 :Question 2 For patients undergoing resting thallium studies, imaging is optimally begun within how many minutes after injection.


Slide 47:Ans.2 within 10-20 minutes after injection.


Question 3 :Question 3 What is the method of 201TI administration?


Slide 49:Ans.3 intravenous injection.


Question 4 :Question 4 The concentration of each radionuclide contaminant changes with time. True or False.


Slide 51:Ans.4 True.


Question 5 :Question 5 What is the Thallium Tl 201, with a physical half-life of Thallium Tl 201?


Slide 53:Ans.5 Thallium Tl 201 has a physical half-life of 73.1 hours.


Question 6 :Question 6 What is a coronary vasodilator that has been employed in 201TI cardiac imaging?


Slide 55:Ans.6 Dipyridamole (Persantine) is a coronary vasodilator that has been employed in 201TI cardiac imaging.


Question 7 :Question 7 The lower energy X-rays obtained from the Mercury Hg 201 daughter of Tl 201 are recommended for myocardial imaging. True or False.


Slide 57:Ans.7 True.


Question 8 :Question 8 Exposure to high levels of thallium can result in harmful health effects. True or False.


Slide 59:Ans.8 True.


Question 9 :Question 9 What is generally proportional to organ blood flow at the time of injection.


Slide 61:Ans.9 Biodistribution is generally proportional to organ blood flow at the time of injection.


Question 10 :Question 10 Thallium Chloride TI201 acts as a what analogue in the body?


Slide 63:Ans.10 Thallium Chloride TI201 acts as a potassium analogue in the body.


References :References Website: http://www.rxlist.com/diseases-conditions-medical-tests/article.htm Book “Nuclear Medicine and PET/CT Technology and Techniques” by Paul E Christian. Sixth edition. Website : http://www.nri.cz/eng/PIL-201-Tl-chlorid.pdf Website: http://rais.ornl.gov/tox/profiles/thallium_ragsa.shtml