Background
Oxygen-15-labelled water (15O-water, [15O]H2O) has specific characteristics that make it an ideal tracer for absolute quantification of myocardial blood flow (MBF). It is a freely diffusible and metabolically inert tracer, that is in contrast with other available PET myocardial perfusion tracers (ie, 13N-ammonia, rubidium-82, and 18F-flurpiridaz) that are metabolically trapped in myocardium. 15O-water has a high extraction fraction of ~1, and the extraction fraction is independent of the actual myocardial blood flow, which means that the tracer uptake rate into myocardium is in linear relationship to the actual MBF. Therefore, there is no “roll-off phenomenon” that might cause underestimation of measured perfusion on high flow rates and subsequent need for using correction factors that may increase noise.
The measurement of MBF using 15O-water is based on tracer’s washin and washout from the myocardium rather than its uptake. As an inert tracer, the retention of 15O-water into myocardium is almost absent, and hence, conventional visual image analysis based on tracer distribution in myocardium is not feasible. However, MBF values measured in small volumes of interest by15O-water PET imaging can be visually presented on parametric standard and polar map images that reflect regional MBF.
Myocardial perfusion imaging with 15O-water PET is in clinical use in an increasing number of centers in Europe. However, it is currently not approved by the U.S. Food and Drug Administration, still limiting its clinical use in the United States.
Description
15O-Water is a very short half-life tracer used in cardiology. It is, in the majority of cases, obtained from local production in centers that do have access to an in-house cyclotron equipped with dedicated targets. Japan is the largest market using 15O-Water, as a consequence of the very high density of hospital-located cyclotrons in this country (almost 200).
Clinical applications
15O-Water is considered as the gold standard flow tracer in myocardial imaging allowing repeat rest and stress MPI with negligible waiting time. 15O-Water is freely diffusible across capillary and cell membranes. The agent accumulates into myocardial cells by extraction that remains linear even at very high flow rates (it is the only perfusion tracer with linear extraction). Results are independent of metabolism and the product delivers low radiation to patients and staff.15O-water is considered to be the most accurate PET flow tracer but image quality is not the best because of the background signal originating from the tracer circulating in the blood pool.
Due to its short half-life, some clinicians prefer 13N-ammonia, but in both cases the half-life remains an issue in terms of supply and only a relative low number of cardiology centers do have access to this molecule.
Dose per patient ranges from 20 to 25 mCi.
Availability
A few centers in Japan or in Finland produce 15O-water on a regular basis, but these patient doses are used on site and all production sites must be considered as local. A center that intends to use 15O-water needs to invest in a cyclotron and a full purification, analysis and dispensing unit.
In January 2021, the company MedTrace Pharma provided information about a new device that automatically produces and administers 15O-water to patients undergoing PET myocardial perfusion imaging. The automate converts on site 15O-gas in 15O-water.
Competition
Alternatives to 15O-water in cardiology include 13N-ammonia, 82Rb-chloride and in SPECT of course the 99mTc-labeled compounds (Sestamibi and tetrofosmin).
Comments
As cardiology is the largest imaging market (but only SPECT), several development approaches are aiming at finding a PET alternative to 15O-Water. The best current solution is the use of 82Rb based on a 82Sr/82Rb generator. Some 18F-labeled molecules for cardiology are still under development (see 18F-Flurpiridaz, 18F-BFPET).