Nitrogen-13 is a radioisotope of nitrogen with a half-life of approximately 10 minutes. It is commonly used in positron emission tomography (PET) imaging to study various physiological processes in the body.
Nitrogen-13 is produced by bombarding oxygen-16 with protons in a cyclotron, resulting in the formation of nitrogen-13 through the nuclear reaction oxygen-16(p,α)nitrogen-13. The resulting nitrogen-13 is then incorporated into radiotracers, such as ammonia or amino acids, for PET imaging studies.
Due to its short half-life, nitrogen-13 is ideal for imaging studies that require rapid imaging and short-lived radiotracers. It is often used to assess myocardial perfusion, evaluate brain function, and study various metabolic processes in the body.
Nitrogen-13 decays by positron emission, which allows for the detection of the emitted positrons and the reconstruction of high-resolution PET images. Its use in PET imaging provides valuable information about the physiological and biochemical processes occurring in living organisms.
Overall, nitrogen-13 plays a crucial role in advancing our understanding of various diseases and conditions through non-invasive imaging techniques, making it a valuable tool in the field of nuclear medicine.
Properties:
Nitrogen-13 (13N) is a very short half-life (9.98 min) positron emitter 100% β+ with an energy of 1,198 keV (100%) corresponding to a maximum annihilation range of 5.4 mm, and an average energy of 492 keV (average annihilation range of 0.4 mm), followed by annihilation producing two gamma rays at 511 keV, decaying into stable carbon-13.
Manufacturing:
13N is produced by proton beam irradiation of 13C in a low-energy cyclotron and is obtained via the route [13C(p,n)13N] at 6-8 MeV. It can also be produced via different routes such as [12C(d,2n)13N] at 2-4 MeV or [16O(p,α)13N] at 6-16 MeV. Usually, chemical processing of the target provides 13N in the form of 13N-ammonia.
Source and availability:
In theory any standard cyclotron equipped with the adequate target is able to produce 13N and 13N-ammonia. In reality there are only a limited number of medical centers that are equipped to produce this radionuclide due to the need for proximity to the patient.
Companies such as NCM-US and Zevacor (SOFIE) are offering access to doses of 13N- ammonia to hospitals located at less than 30 min transportation distance from some of their equipped manufacturing sites.
The TRIUMF center which is equipped with a line connection between the cyclotron and the neighboring British Columbia University hospital is equipped with a 3 km transfer line that allows supply of radiodiagnostic agent in about 2 min. This is an example of a viable technical solution for short-lived isotope transfer also applicable to 13N.
13N is well developed in Japan with a high number of centers using this tracer as an alternative to SPECT in cardiology imaging.
Derivatives:
The only useful 13N derivative is 13N-ammonia in cardiology. 13N-ammonia is an ideal flow tracer allowing repeat rest and stress MPI with negligible waiting time. The specific Japanese regulation (the cyclotrons need to be within a medical unit and close to the cameras) has led to the emergence of 13N use (like for 15O-Water) in this country.
Price:
As 13N is directly produced on site and each batch is rarely used in more than one patient, the dose per patient is actually the dose per batch. Although irradiation and synthesis times remain short, one must consider that the overall operator and radiochemist times must be integrated in total to the cost of the dose on top of raw material, energy and amortization. Roughly a single dose of 13N-ammonia generates cost of goods in the range of EUR 600–800 (US$ 780-1,000). The amount of 13N-ammonia in a dose does not affect these figures. Profit can be made either if a cyclotron is in overcapacity anyway or if the manufactured dose can be split among several customers.
Issues:
- Major issues of 13N-ammonia are linked to its short half-life.
Comments:
Cardiologists over the world would be really interested in ammonia, but the difficulty in accessing to this radionuclide and the cost of the equipment has discouraged most of the physicians (with the exception of Japan). Actually, for routine PET applications in cardiology, 82Rb, associated to its 82Sr/82Rb generator, proved to be the best solution. Questioning about the competition between 13N-ammonia, 15O-water and 82Rb-chloride was relevant as long as access to 82Rb was an issue, but new manufacturing solutions are now in place and 82Rb became available at a much larger extent, at least in the US starting in 2017 (competition between Bracco and Jubilant-Draximage). This will definitely only leave a role in R&D programs for ammonia (outside of Japan).