Oxygen-15 is a radioisotope, often used in positron emission tomography (PET). It can be used in, among other things, water for PET myocardial perfusion imaging and for brain imaging. It has an atomic mass of 15.0030656(5), and a half-life of 122.266(43) s. It is produced through deuteron bombardment of nitrogen-14 using a cyclotron.
Properties:
Oxygen-15 (15O) is a radionuclide emitter of positrons (100% average energy at 735 keV, corresponding to an average annihilation distance of 1.1 mm and a maximum energy at 1,732 keV corresponding to a maximum annihilation distance of 8.0 mm), followed by annihilation producing two gamma rays at 511 keV, with a very short half-life of 2.03 min, decaying into stable nitrogen-15.
Manufacturing:
Due to their half-lives, the radionuclide 15O is generally used at the site of production. In general, low-energy nuclear reactions like (p,n), (p,α), (d,n), and (d,α) are used and a small-sized cyclotron is adequate for the production of this radionuclide. The excitation functions have been measured systematically. The thick target yield over the optimum energy range for the production of each radionuclide is well known.
There are two ways to produce 15O, both through a low-energy cyclotron, either starting from 15N with proton bombardment [15N(p,n)15O] at 5-8 MeV or from 14N with deutons bombardment [14N(d,n)15O] at 3-7 MeV.
Source and availability:
In theory any standard cyclotron equipped with the adequate target is able to produce 15O and 15O-Water. 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.
The cyclotron of the TRIUMF center is equipped with a 3 km long transfer line that allows supply of short half-life radiodiagnostic to the neighboring British Columbia University hospital with transfer times lower than 2 min. This transfer line is even used for clinical applications with 15O-Water.
For production of 15O, generally pressurized gas targets in batch mode are used. The product activity is removed from the target by simple expansion and led to vessels where conversion to other chemical forms suitable for labeling of organic compounds is done. The chemical form of the activity leaving the target depends upon the additive given to the gas in the target. The resulting 15O from an N2(O2) target, for example, is [15O]O2. The most reliable production of 15O demands a deuteron beam at the cyclotron. If it is not available, the (p,n) reaction on highly enriched 15N is utilized. An efficient recovery system for the enriched target gas must then be incorporated in the target system.
Derivatives:
Oxygen is the third most common atom in organic molecules after hydrogen and carbon, so any molecule labeled with a radioactive oxygen atom could play an important role in the description and follow-up of the biological cell mechanisms. Unfortunately, with its 2 min half-life, 15O is the oxygen radioisotope with the longest half-life in this group. As a consequence, oxygen is not useful in these processes.
Only the simplest chemical entities can be produced labeled with 15O, such as 15O-O2 gas or 15O-Water. These molecules do not really interfere with the biological processes and are mainly used to follow fluid transfers between cells. In fact, 15O-Water is the only molecule that has found some applications, mainly in cardiology, but it also became the gold standard in this discipline. 15O is used in cerebral and myocardial blood flow imaging.
The specific Japanese regulation (the cyclotrons need to be within a medical unit and close to the cameras) has led to the emergence of 15O use (like for 13N-Ammonia) in this country.
15O was used integrated in small molecules such as 15O-CO, 15O-CO2, 15O-Water, and 15O-oxygen (gas).
Price:
As 15O is directly produced on site and each batch can only be used for one single 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 15O-water has cost of goods estimated at about EUR 500–700 (US$ 650-900). Profit could be expected if dedicated cyclotrons were run with private staff in hospitals with high patient throughput. This is definitely not a good business opportunity and the only way to make a business out of 15O will be to develop and sell dedicated cyclotrons to clinical research centers.
Issues:
◼ Need for a dedicated cyclotron nearby. Japan, with its high number of cyclotrons is an exception and has developed a network of tools able to produce both 13N and 15O.
◼ Very short half-life.
Comments:
15O-water is considered by cardiologists as the gold standard in myocardial perfusion imaging. However, the difficulty accessing this tracer leaves little room for a large market. Moreover, the new solution for manufacturing of the 82Rb generator will definitely lead the cardiologists interested in PET imaging to consider only this later. There is no real future for 15O-water in cardiology except as a research tool in dedicated centers (or in countries such as Japan which have different regulatory constraints).
