Ammonia N-13

Name: Ammonia N-13

Indications and Usage for Ammonia N-13

Ammonia N 13 Injection, USP is indicated for diagnostic Positron Emission Tomography (PET) imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease.

Drug Interactions

The possibility of interactions of Ammonia N 13 Injection with other drugs taken by patients undergoing PET imaging has not been studied.

Use in specific populations

Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with Ammonia N 13 Injection. It is also not known whether Ammonia N 13 Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Ammonia N 13 Injection should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for radiation exposure to nursing infants from Ammonia N 13 Injection, use alternative infant nutrition sources (e.g. stored breast milk or infant formula) for 2 hours (>10 half-lives of radioactive decay for N 13 isotope) after administration of the drug or avoid use of the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of Ammonia N 13 Injection has been established in pediatric patients based on known metabolism of ammonia, radiation dosimetry in the pediatric population, and clinical studies in adults [see Dosage and Administration (2.4)].

Ammonia N-13 Description

Chemical Characteristics

Ammonia N 13 Injection, USP is a positron emitting radiopharmaceutical that is used for diagnostic purposes in conjunction with positron emission tomography (PET) imaging. The active ingredient, [13N] ammonia, has the molecular formula of 13NH3with a molecular weight of 16.02, and has the following chemical structure:

Ammonia N 13 Injection, USP is provided as a ready to use sterile, pyrogen-free, clear and colorless solution. Each mL of the solution contains between 0.138 GBq to 1.387 GBq (3.75 mCi to 37.5mCi) of [13N] ammonia, at the end of synthesis (EOS) reference time, in 0.9% aqueous sodium chloride. The pH of the solution is between 4.5 and 7.5. The recommended dose of radioactivity (10-20 mCi) is associated with a theoretical mass dose of 0.5-1.0 picomoles (8.47-16.94 picograms) of ammonia.

Physical Characteristics

Nitrogen N13 decays by emitting positron to Carbon C13 (stable) and has a physical half-life of 9.96 minutes. The principal photons useful for imaging are the dual 511 keV gamma photons that are produced and emitted simultaneously in opposite direction when the positron interacts with an electron (Table 2).

Table 2: Principal Radiation Emission Data for Nitrogen 13
Radiation/Emission % Per Disintegration Energy
* Produced by positron annihilation
Positron(β+) 100 1190 keV (Max.)
Gamma(±)* 200 511 keV

The specific gamma ray constant (point source air kerma coefficient) for nitrogen N13 is 5.9 R/hr/mCi (1.39 × 10-6Gy/hr/kBq) at 1 cm. The half-value layer (HVL) of lead (Pb) for 511 keV photons is 4 mm. Selected coefficients of attenuation are listed in Table 3 as a function of lead shield thickness. For example, the use of 39 mm thickness of lead will attenuate the external radiation by a factor of about 1000.

Table 3: Radiation Attenuation of 511 keV Photons by lead (Pb) shielding
Shield Thickness (Pb) mm Coefficient of Attenuation
4 0.5
8 0.25
13 0.1
26 0.01
39 0.001
52 0.0001

Table 4 lists fractions remaining at selected time intervals from the calibration time. This information may be used to correct for physical decay of the radionuclide.

Table 4: Physical Decay Chart for Nitrogen N 13
Minutes Fraction Remaining
*Calibration time
0 1.00
5 0.706
10 0.499
15 0.352
20 0.249
25 0.176
30 0.124

Ammonia N-13 - Clinical Pharmacology

Mechanism of Action

Ammonia N 13 Injection is a radiolabeled analog of ammonia that is distributed to all organs of the body after intravenous administration. It is extracted from the blood in the coronary capillaries into the myocardial cells where it is metabolized to glutamine N 13 and retained in the cells. The presence of ammonia N 13 and glutamine N 13 in the myocardium allows for PET imaging of the myocardium.

Pharmacodynamics

Following intravenous injection, ammonia N 13 enters the myocardium through the coronary arteries. The PET technique measures myocardial blood flow based on the assumption of a three-compartmental disposition of intravenous ammonia N 13 in the myocardium. In this model, the value of the rate constant, which represents the delivery of blood to myocardium, and the fraction of ammonia N 13 extracted into the myocardial cells, is a measure of myocardial blood flow. Optimal PET imaging of the myocardium is generally achieved between 10 to 20 minutes after administration.

Pharmacokinetics

Following intravenous injection, Ammonia N 13 Injection is cleared from the blood with a biologic half-life of about 2.84 minutes (effective half-life of about 2.21 minutes). In the myocardium, its biologic half-life has been estimated to be less than 2 minutes (effective half-life less than 1.67 minutes).

The mass dose of Ammonia N 13 Injection is very small as compared to the normal range of ammonia in the blood (0.72-3.30 mg) in a healthy adult man [see Description (11.1)].

Plasma protein binding of ammonia N 13 or its N 13 metabolites has not been studied.

Ammonia N 13 undergoes a five-enzyme step metabolism in the liver to yield urea N 13 (the main circulating metabolite). It is also metabolized to glutamine N 13 (the main metabolite in tissues) by glutamine synthesis in the skeletal muscles, liver, brain, myocardium, and other organs. Other metabolites of ammonia N 13 include small amounts of N 13 amino acid anions (acidic amino acids) in the forms of glutamate N 13 or aspartate N 13.

Ammonia N 13 is eliminated from the body by urinary excretion mainly as urea N 13.

The pharmacokinetics of Ammonia N 13 Injection have not been studied in renally impaired, hepatically impaired, or pediatric patients.

References

  1. Annals of the ICRP. Publication 53. Radiation dose to patients from radiopharmaceuticals. New York: Pergamon Press, 1988.
  2. Demer, L.L.K.L.Gould, R.A.Goldstein, R.L.Kirkeeide, N.A.Mullani, R.W. Smalling, A.Nishikawa, and M.E.Merhige. Assessment of coronary artery disease severity by PET: Comparison with quantitative arteriography in 193 patients. Circulation 1989; 79: 825-35.
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