THALLOUS CHLORIDE Tl 201

Handle Thallous Chloride Tl 201 Injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions ( 5.3)] . Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling Thallous Chloride Tl 201 Injection.

Radiopharmaceuticals should be used by or under the control of healthcare providers who are qualified by specific training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the appropriate governmental agency authorized to license the use of radionuclides.

Myocardial Perfusion Imaging in Adults

• Planar scintigraphy: 37 MBq to 74 MBq (1 mCi to 2 mCi) administered intravenously
• SPECT: 74 MBq to 111 MBq (2 mCi to 3 mCi) administered intravenously

Parathyroid Hyperactivity Localization in Adults

Planar or SPECT: 75 MBq to 130 MBq (2 mCi to 3.5 mCi) administered intravenously

Patient Preparation
Instruct patients to hydrate before and after Thallous Chloride Tl 201 Injection administration and to void before imaging and frequently thereafter following Thallous Chloride Tl 201 Injection administration [see Warnings and Precautions ( 5.3)] .

Administration

• Use aseptic technique and radiation shielding when withdrawing and administering Thallous Chloride Tl 201 Injection.
• Visually inspect the drug for particulate matter and discoloration prior to administration, whenever the solution and container permit. Do not use if contents are turbid or discolored.
• Measure the patient dose with a dose calibrator immediately prior to administration.
• Use within 6 days from the manufacturer’s calibration date or 9 days from the date of manufacture, whichever comes first.
• Dispose of unused products in a safe manner in compliance with applicable regulations.

Myocardial Perfusion Imaging
For resting myocardial studies, begin imaging 10 minutes to 20 minutes after administration of Thallous Chloride Tl 201 Injection. Target-to-background ratios are improved when patients are injected upright and in the fasting state; the upright position reduces the hepatic and gastric thallium-201 concentration.

For exercise stress testing, administer Thallous Chloride Tl 201 Injection at the start of a period of maximum stress, which is sustained for approximately 30 seconds after injection. Begin imaging within 10 minutes after administration to obtain maximum target-to-background ratios. Within 2 hours after the completion of the stress testing, the target-to-background ratios may decrease in lesions that are attributable to transient ischemia.

Parathyroid Hyperactivity Localization
For localization of parathyroid hyperactivity, administer Thallous Chloride Tl 201 Injection before, with, or after a minimal dose of a thyroid imaging agent such as sodium pertechnetate Tc 99m injection or sodium iodide I 123 capsules to enable thyroid subtraction imaging.

Estimated absorbed radiation doses from an intravenous injection of Thallous Chloride Tl 201 Injection are shown in Table 1.

¹Assumed percentage of 98.3% thallium-201, 0.3% thallium-200, 1.2% thallium-202, and 0.2% lead-203

Thallous Chloride Tl 201 Injection may cause anaphylactic reactions characterized by cardiovascular, respiratory, and cutaneous symptoms [see Adverse Reactions ( 6)] . Have resuscitation equipment and trained staff readily available.

Induction of cardiovascular stress might be associated with serious adverse reactions such as myocardial infarction, arrhythmia, hypotension or hypertension, ECG abnormalities, chest pain, bronchoconstriction, and cerebrovascular events [see Adverse Reactions ( 6)] . Perform stress testing in the setting where cardiac resuscitation equipment and trained staff are readily available. Perform pharmacologic stress in accordance with the pharmacologic stress agent’s prescribing information.

Thallous Chloride Tl 201 Injection contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling to minimize radiation exposure to patients and health care providers. Advise patients to hydrate before and after administration and to void frequently after administration  [see Dosage and Administration ( 2.1,  2.3)].

Injection site reactions and extravasation have been reported after administration of Thallous Chloride Tl 201 Injection [see Adverse Reactions ( 6)] . Administer Thallous Chloride Tl 201 Injection strictly into the vein to avoid local tissue accumulation and irradiation. Confirm intravenous patency before injection.

Risk Summary

There are no data on Thallous Chloride Tl 201 Injection use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Studies using human placentas demonstrate that thallous chloride Tl 201 crosses the placenta. No animal reproductive studies have been conducted.

All radiopharmaceuticals, including Thallous Chloride Tl 201 Injection have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. If considering administration of Thallous Chloride Tl 201 Injection to a pregnant woman, inform the patient about the potential for adverse pregnancy outcomes based on the radiation dose from Thallous Chloride Tl 201 Injection and gestational timing of exposure.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 3% and 10% to 20%, respectively.

Risk Summary

Thallous chloride Tl 201 has been detected in the milk of lactating women. There are no data on the effects of thallous chloride Tl 201 on milk production or the effects of thallous chloride Tl 201 on the breastfed infant.

Exposure of the breastfed infant to thallous chloride Tl 201 can be minimized by advising a lactating woman to temporarily discontinue breastfeeding and pump and discard milk for a minimum of 96 hours after administration of Thallous Chloride Tl 201 Injection. Minimize close contact with infants if the administered dose would result in an effective dose greater than 1 mSv to the infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Thallous Chloride Tl 201 Injection and any potential adverse effects on the breastfed infant from Thallous Chloride Tl 201 Injection or from the underlying maternal condition.

The safety and effectiveness of Thallous Chloride Tl 201 Injection in pediatric patients have not been established.

Clinical studies of Thallous Chloride Tl 201 Injection for myocardial perfusion imaging did not include sufficient numbers of subjects aged younger than 65 years to determine whether they respond differently from younger subjects. Other reported experience has not revealed clinically relevant differences in the response of elderly in comparison to younger patients.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Thallous Chloride Tl 201 Injection is a sterile, radioactive diagnostic drug for intravenous use.

Each mL contains 37 MBq (1 mCi) thallous chloride Tl 201 at calibration time and the following inactive ingredients: 9 mg sodium chloride and 0.9% (v/v) benzyl alcohol. The pH is adjusted to between 4.5 to 7.0 with hydrochloric acid and/or sodium hydroxide.

Thallium-201 is cyclotron produced. At the time of calibration it contains no more than 1% thallium-200, no more than 1% thallium-202, no more than 0.25% lead-203, and no less than 98% thallium-201 as a percentage of total activity. No carrier has been added.

The concentration of each radionuclidic contaminant changes with time. Figure 1 shows maximum concentration of thallium-200 (Tl 200) and thallium-202 (Tl 202) radionuclidic contaminants as a function of time.

Figure 1. Radionuclidic Contaminants 

figure 1

Thallium-201, with a physical half-life of 72.9 hours, decays by electron capture to mercury-201. Photons that are useful for detection and imaging are listed in Table 2. The lower energy x-rays obtained from the mercury-201 daughter of thallium-201 are recommended for myocardial imaging, 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.

The specific gamma ray constant for thallium-201 is 0.45 R/mCi-hr at 1 cm. The first half-value thickness of lead (Pb) is 0.026 cm. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 3. For example, the use of 0.194 cm of lead will decrease the external radiation exposure by a factor of about 1,000.

To correct for physical decay of the radionuclide, the fractions that remain at selected intervals after calibration time are shown in Table 4.

* Calibration Time

Thallous chloride Tl 201 with no carrier added accumulates in viable myocardium in a manner analogous to that of potassium. Experiments in healthy subjects using labeled microspheres have shown that the myocardial distribution of thallous chloride Tl 201 correlates with regional perfusion.

In clinical studies, Thallous Chloride Tl 201 images have been found to visualize areas of infarction as “cold” or nonlabeled regions that were confirmed by electrocardiographic and enzyme changes. 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. Anatomic configurations may interfere with visualization of the right coronary artery territory.

The pharmacodynamics of thallous chloride Tl 201 have not been established.

Distribution
After intravenous administration, thallous chloride Tl 201 clears from the blood with maximal concentration in normal myocardium occurring at about 10 minutes. It will, in addition, localize in parathyroid adenomas; it is not specific since it will localize to a lesser extent in sites of parathyroid hyperplasia and other abnormal tissues such as thyroid adenoma, neoplasia (e.g., parathyroid carcinoma), and sarcoid. Biodistribution is generally proportional to organ blood flow at the time of injection. Blood clearance of thallous chloride Tl 201 is primarily by the myocardium, thyroid, liver, kidneys, and stomach with the remainder distributing fairly uniformly throughout the body. The dosimetry data in Table 1 reflect this distribution pattern and are based on a biological half-life of 2.4 days.

Elimination
Five minutes after intravenous administration only 5% to 8% of injected activity remained in the blood. A biexponential disappearance curve was obtained, with 91.5 % of the blood radioactivity disappearing with a half-time of about 5 minutes. The remainder had a half-time of about 40 hours.

Excretion
Approximately 4% to 8% of the injected dose was excreted in the urine in the first 24 hours. The whole body disappearance half-time was 9.8 ± 2.5 days. Kidney concentration was found to be about 3% of the injected activity and the testicular content was 0.15%. Net thyroid activity was determined to be only 0.2% of the injected dose, and the activity disappeared in 24 hours. From anterior and posterior whole-body scans, it was determined that about 45% of the injected dose was in the large intestines and contiguous structures (liver, kidneys, abdominal musculature).

No long-term animal studies have been performed to evaluate carcinogenic potential, mutagenic potential, or whether this drug affects fertility in males or females.