Figure 11. [13N]-AMMONIA

Usage of 13N-ammonia with PET-CT enables an accurate, noninvasive quantification of regional myocardial perfusion. Its kinetic properties can be described in terms of a three-compartment model:

VASCULAR COMPARTMENT: characterizes the concentration of N-13 ammonia in  arterial blood

INTERSTITIAL COMPARTMENT: a conceptual space used to represent the extracellular N-13 ammonia in myocardial tissue.

CELLULAR COMPARTMENT: represents the accumulation of N-13 glutamine within the myocyte.

This model was developed under the following set of assumptions:

• The term “ammonia” refers to NH3 in chemical equilibrium with its charged species NH4+ (ammonium).

• 13N-ammonia behaves like a freely diffusible tracer across plasma and cell membranes.

• The extracellular and intracellular 13N-ammonia pools rapidly equilibrate.

• In bloodstream, 13N-ammonia exists primarily as NH4+, which can substitute for K+ on the sodium-potassium transmembranous exchange system, it thus may be actively transported into myocardium.

• Inside the myocyte NH4+ is converted to 13N-glutamine by glutamine synthetase and progressively accumulates. This process represents the main route for metabolic trapping and fixation of 13N-ammonia (and in a lesser degree, the ketoglutarate-glutamic acid reaction). Glutamine is then slowly released from the cell and serves as a carrier of ammonia for excretion.

• The available glutamine synthetase level remains essentially unchanged, so the ammonia molecules converted to glutamine remain constant.

• Both uptake and retention of 13N-ammonia in myocardium are primarily related to myocardial blood flow, therefore, at higher flows more 13N-ammonia diffuses back into the intravascular compartment and the fraction retained in the myocardium declines.
• Overall trapping of 13N-ammonia relies on intact metabolism, which may be impaired in ischemia and high cardiac work.

- Machac J; Radiopharmaceuticals for Clinical Cardiac PET Imaging; Cardiac PET and PET/CT Imaging; Springer; 2007; pp 73-82

- Muzik O, et al; Validation of Nitrogen-13-Ammonia Tracer Kinetic Model for Quantification of Myocardial Blood Flow Using PET; J Nucl Med. 1993;34:83-91.

- Hutchins GD, et al; Noninvasive quantification of regional blood flow in the human heart using N-13 Ammonia and dynamic PET imaging; JACC Vol 15, No. 5, 1990:1032-42

- Schelbert HR, et al; N-13 ammonia as an indicator of myocardial blood flow; Circulation. 1981;63:1259-1272