Patent Application
20050279130
1. Field of Invention
This invention generally relates to production of radionuclides, particularly a technique for refilling [18O]oxygen in a system for producing [18F]fluorine gas.
2. Description of Related Art
Positron emission tomography (PET) is a medical imaging technique for measuring the concentrations of positron-emitting radiopharmaceuticals within the tissue of living subjects. Radiopharmaceuticals prepared from cyclotron-produced fluorine-18 radionuclide have found widespread use in a variety of PET biological probes for research and clinical investigations of the brain, heart, and in the diagnosis of cancer. In a typical PET procedure, the radiopharmaceutical is administered to the bloodstream of a subject and the distribution of positron activity emitted from the radiopharmaceutical in vivo is then measured by emission tomography as a function of time. A computerized reconstruction procedure is implemented to produce tomographic images of the tissue as it interacts with the radiopharmaceutical.
Synthesis of fluorine-18 in the form of [18F]fluorine gas is a significant step in PET studies. Because the half-life of fluorine-18 is approximately 109.8 minutes, PET operators prefer to have a fluorine-18 producing cyclotron on-site so as to avoid losing a significant fraction of the produced isotope during transportation.
Conventional production of [18F]fluorine gas typically employs a “two-shot” process using a cyclotron generated proton beam and a target containing 18O2. See, e.g., R. J. Nickles et al., An 18O2 Target for the Production of [18F]F2, Int. J. Appl. Radiat. Isot., Vol. 35, No. 2, 117-122 (1984); A. Bishop et al., Proton Irradiation of [18O]O2: Production of [18F]F2 and [18F]F2+[18F]OF2, Nuclear Medicine & Biology, Vol. 23, 189-199 (1996); and A. D. Roberts et al., Development of An Improved Target for [18F]F2 Production, Appl. Radiat. Isot., Vol. 46, No. 2, 87-91 (1995), the disclosures of which are incorporated herein by reference in their entirety. In a “two-shot” production process, an oxygen gas target enriched with the isotope 18O2 is first bombarded (shot) with a cyclotron produced 16.5 MeV proton beam of 40 μA for approximately 45 min. During this first shot, the protons from the cyclotron collide with the [18O]O2 gas molecules, thereby causing a 18O(p,n)18F nuclear reaction that produces negatively charged 18F ions. These 18F(−) ions adhere to the walls of the target and a second bombardment (shot) of protons is needed to “wash out” the radioactive fluorine. In this second shot, the [18O] isotope enriched oxygen gas in the target volume is removed by cryogenic cooling and replaced with a mixture of 0.1 to 2% F2 (cold, i.e., non-radioactive, F2) and argon (Ar), which is subsequently irradiated with another cyclotron produced 16.5 MeV proton beam of 35 μA for 20 minutes. The second bombardment of the Ar and cold F2 succeeds in forcing a fluorine exchange that results in useful levels of [18F]F2 in the gas phase.
Moreover, economic considerations also drive operators to efficiently use and conserve isotopically enriched [18O]oxygen gas, from which [18F]fluorine gas is synthesized. The enriched [18O]oxygen gas is expensive and must be handled with great care. It is also sold in rather small quantities and on usage it is important to be able to empty the whole enriched oxygen gas bottle into an appropriate reservoir of the [18F]F2 production facility. Decreasing the oxygen reservoir volume improves the overall safety of the production facility and mitigates risk of loosing or contaminating large amounts of oxygen gas once it is in the system.
During the production of [18F]fluorine gas as noted above, there is a risk of filling the reservoir with too much or too little [18O]oxygen gas. Too much [18O]oxygen gas is wasteful and could potentially damage the reservoir as well as other components within the [18F]fluorine production system. Too little [18]oxygen gas will not enable the reservoir to provide enough [18O]oxygen to produce a useful amount of [18F]F2. The development of a more reliable and safe technique for repeatedly delivering a precise amount of [18O]oxygen to the reservoir would be greatly beneficial.
The present invention overcomes these and other deficiencies of the prior art by providing an intermediate container in the [18O]oxygen refilling system having a volume defined by the liquid equivalent of a predefined volume, pressure, and temperature of [18O]oxygen gas.
In at least one embodiment of the invention, a refilling apparatus comprises a first fluid container, a second fluid container, and an interface for coupling the first and second fluid containers to a supply of gas, wherein the first fluid container has a volume corresponding to a certain amount of liquid condensed from the gas, which upon phase transformation provides a desired gas pressure within an entire volume of the first and second fluid containers. The first fluid container is preferably a coil of tubing for submersion into a bath of liquid nitrogen to cryogenically cool the first fluid container, thereby condensing the gas into liquid form. A motor can be included to move the coil of tubing in and out the bath of liquid nitrogen at appropriate times. The apparatus is particularly well-suited for providing [18O]oxygen gas to a [18O]O2/F2 target system. The desired pressure is ideally based upon the apparatus supplying the [18O]O2/F2 target system with an appropriate amount of [18O]oxygen gas for a predetermined number of production runs. The desired gas pressure resulting from operation of the apparatus is preferably between 40 to 50 bar.
In at least one embodiment of the invention, a method comprises the steps of cryogenically cooling a first fluid container and supplying a gas to the cryogenically cooled first fluid container, wherein the gas condenses into liquid form within the cryogenically cooled first fluid container. Upon the first fluid container becoming full of the condensed liquid, the method further includes the steps of warming the first fluid container to transform the condensed liquid into gas, and allowing the transformed gas to expand into a second fluid container. The resulting transformed gas has a desired gas pressure within a total volume of the first and second fluid containers based upon the full volume of the condensed liquid in the first fluid container. The first fluid container is preferably a coil of tubing for submersion into a bath of liquid nitrogen to cryogenically cool the tubing and condense the gas into liquid form. To transform the liquid back into gas, the applied bath of liquid nitrogen is removed from the first fluid container. The process is ideally suited for [18O]oxygen gas for use in a [18O]O2/F2 target system that produces [18F]fluorine gas.
One advantage of the exemplary embodiments of the present invention is that it provides a reliable and safe technique for repeatedly delivering a precise amount of [18O]oxygen to a gas reservoir within a refilling system.
Another advantage of the exemplary embodiments of the present invention is that it mitigates, if not eliminates, the risk of over filling a reservoir with too much [18O]oxygen. Moreover, exemplary embodiments of the invention can maintain the highest possible gas purity since no equipment (e.g. vacuum pump) interferes with the gas during the refilling process.
The foregoing, and other features and advantages, will be apparent from the following, more particular description of the preferred embodiments of the invention, the accompanying drawings, and the claims.
For a more complete understanding of the present invention, the objects and advantages thereof, reference is now made to the following descriptions taken in connection with the accompanying drawings in which:
Preferred embodiments of the invention and their advantages may be understood by referring to
Referring to
Parameters relevant to the design of the target volume 120 for fluorine isotope production are the beam strike volume, geometry, and material. Although not the focus of the present invention, it is worthy to note that different target volumes can be implemented as target volume 130 and variations in design of the target volume 120 can influence the amount of overall [18F]F2 recovered in system 100. Target volumes for the 18O(p,n)18F reaction can be implemented using conical or straight bore shapes, beam entrance diameters of 10-15 mm, beam exit diameters of 10-23 mm, and volumes of 7.9-14.6 cc. Target volume 120 can be constructed from materials such as, but not limited to aluminum, silver, copper, nickel, or gold plated copper.
The washout mixture is provided by the argon reservoir 140 and the Ar/F2 reservoir 150. These reservoirs 140 and 150 can each be implemented as a replaceable tank or a refillable reservoir having an input (not shown) for coupling the reservoir to an external supply of gas. Although argon is preferable, other noble gases can be used such as krypton (Kr) or neon (Ne). The Ar/F2 reservoir 150 can be optionally coupled to an activated sodium-fluorine (NaF) trap 155 to remove any possible hydrogen fluoride contamination from the reservoir 150.
The pump 160 can be any type of conventional vacuum pump, the identification and implementation of which is apparent to one of ordinary skill in the art. An optional soda lime trap 165 can be coupled to the pump 160 to prevent harmful F2 from contaminating the vacuum pump oil and escaping through the vacuum exhaust.
Valves A-I can each include a solenoid remotely controlled by CPU and/or a manual valve. These valves A-I open and close at varying times to allow the appropriate pressurized gases to flow to and from the various components among the system 100 as described herein. The components in system 100 (excluding cyclotron 110) are coupled to one another by way of appropriate conduits, e.g., pipes and/or tubing, the identification and implementation of which are apparent to one of ordinary skill in the art, in order to transport the various gases. One of ordinary skill in the art recognizes that other components such as pressure monitors can be coupled to the system 100 as deemed necessary.
Referring to
The intermediate container 220 is provided to ensure that a predefined volume of [18O]oxygen gas is filled into the refilling apparatus 130. Particularly, the intermediate container 220 has a volume selected so that when it is full of [18O]oxygen in liquid form, that liquid when changed to gas equals the necessary amount and pressure of [18O]oxygen gas to fill the oxygen refilling apparatus 130 with sufficient gas (but not overloading the system) to last for a selected number of [18F]fluorine production runs at ambient temperature. In other words, the volume of the intermediate container 220 is based on the desired [18O]oxygen gas volume and pressure, but in liquid phase. The liquid nitrogen dewar 230 is used to cool the intermediate container 220 to 77°K. so that the [18O]oxygen gas condenses into a liquid. The liquid nitrogen dewar 230 is preferably coupled to a motor that enables the dewar 230 to place a bath of liquid nitrogen in and out of contact with the intermediate container 220. The intermediate container 220 is preferably shaped as coiled tubing in order to maximize the surface area in contact with the liquid nitrogen, thereby expediting the cooling process. However, geometries other than coiled tubing such as, but not limited to a cylinder can be implemented. The intermediate container 220 can be designed to last for hundreds of productions runs and to provide the operator with a safe, repeatable, and reliable process.
Referring to
Valve I is placed near the [18O]oxygen bottle 205, from which a selected amount of gas (determined by the volume of intermediate container 220) will be cryocooled. It is preferred not to have any valve between reservoir 210 and intermediate container 220 since when the gas expands, there should be a volume for it to expand in. Otherwise, the intermediate container 220 and possibly the two-shot [18O]O2/F2 target system 100 may be put under a very large pressure and the tubes, connections, and valves could break.
The parameter values attributed to the proton beams, e.g., energy, current, and time, as well as the values attributed to the volume and pressures of the various gases and containers are exemplary only. One of ordinary skill in the art recognizes that these parameters can vary as deemed necessary or desired.
Although the invention has been particularly shown and described with reference to several preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined in the appended claims.
