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Thallous Tl (Thallous Chloride, TL-201) - Description and Clinical Pharmacology

 
 



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DESCRIPTION

Chemical Characteristics

Thallous Chloride Tl 201 Injection is supplied in an isotonic solution as a sterile, non-pyrogenic diagnostic radiopharmaceutical for intravenous administration. Each milliliter contains 37 MBq (1 mCi) Thallous Chloride
Tl 201 at calibration time, made isotonic with 9 milligrams sodium chloride and preserved with 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 Tl 201 is cyclotron produced. At the time of calibration it contains no more than 1.0% Thallium Tl 200, no more than 1.0% Thallium Tl 202, no more than 0.25% Lead Pb 203, and no less than 98% Thallium Tl 201 as a percentage of total activity. No carrier has been added.

It is recommended to administer Thallous Chloride Tl 201  Injection close to calibration time to minimize the effect of higher levels of radionuclidic contaminants present at pre- and post-calibration dates. The concentration of each radionuclidic contaminant changes with time. Figure 1 shows maximum concentration of each radionuclidic contaminant as a function of time.

Figure 1. Radionuclidic Contaminants

Physical Characteristics

Thallium Tl 201, with a physical half-life of 72.9 hours, decays by electron capture to mercury Hg 201. Photons that are useful for detection and imaging are listed in Table 3. The lower energy x-rays obtained from the mercury Hg 201 daughter of thallium Tl 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.

Table 3. Principal Radiation Emission Data

Radiation

Mean Percent/
Disintegration

Energy
(keV)

Gamma-4

2.7

135.3

Gamma-6

10.0

167.4

Mercury

x-rays

94.4

68.9-80.3

From: 3Stabin MG, da Luz CQPL. New Decay Data for Internal and External Dose Assessment, 2002, Health Phys. 83(4):471-475.

External Radiation

The specific gamma ray constant for thallium Tl 201 is 4.64 R/mCi-hr at
1 cm. The first half-value thickness of lead (Pb) is 0.0006 cm. A range of values for the radiation emitted by this radionuclide with the corresponding exposure rate at 1 cm that results from interposition of various thicknesses of lead is shown in Table 4. For example, the use of 0.21 cm of lead will decrease the external radiation exposure by a factor of about 1,000.

Table 4. Radiation Attenuation by Lead Shielding

cm of
Lead (Pb)

Coefficient of

Attenuation

0.0005

0.5

0.026

10-1

0.081

10-2

0.18

10-3

0.31

10-4

Data supplied by Oak Ridge Associated Universities, Radiopharmaceutical Internal Dose Information Center, Oak Ridge, TN, 1994. Includes 10 keV x-rays4.

To correct for physical decay of the radionuclide, the fractions that remain at selected intervals after calibration time are shown in Table 5.

Table 5. Thallium Tl 201 Decay Chart; Half-Life 72.9 Hours

Hours

Fraction

Remaining

Hours

Fraction

Remaining

0*

1.00

66

0.53

6

0.95

72

0.50

12

0.89

78

0.48

18

0.84

84

0.45

24

0.80

90

0.43

30

0.75

96

0.40

36

0.71

108

0.36

42

0.67

120

0.32

48

0.63

132

0.29

54

0.60

144

0.25

60

0.57

    * Calibration Time

CLINICAL PHARMACOLOGY

Mechanism of Action

Thallous Chloride Tl 201 with no carrier added accumulates 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 correlates well with regional perfusion.

In clinical studies, Thallous Chloride Tl 201 images have been found to visualize areas of infarction as “cold” or nonlabeled regions which are 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 was administered in conjunction with an exercise stress test. Anatomic configurations may interfere with visualization of the right coronary artery.

Pharmacokinetics

After intravenous administration, Thallous Chloride Tl 201 clears rapidly from the blood with maximal concentration by 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. Thallous Chloride Tl 201 is excreted slowly and to an equal extent in both feces and urine.

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

Approximately 4 to 8 percent 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 percent of the injected activity and the testicular content was 0.15 percent. Net thyroid activity was determined to be only 0.2 percent of the injected dose, and the activity disappeared in 24 hours. From anterior and posterior whole-body scans, it was determined that about 45 percent of the injected dose was in the large intestines and contiguous structures (liver, kidneys, abdominal musculature).

NONCLINICAL TOXICOLOGY

Carcinogenesis, Mutagenesis, Impairment of Fertility

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

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