Patent Grant
7858374
The instant invention relates generally to nuclear medicine and radio-labeled isotopes, and more specifically, to a method and device for reducing CO2 to CO using metal oxide and synthesizing positron emitter radio-labeled molecular imaging probes comprising [11C]CO or [15O]CO as the positron emitter radio-label.
Positron Emission Tomography (PET) is a powerful tool for diagnosing a number of health related conditions and detection of disease. Generally, PET imaging systems create images based on the distribution of positron-emitter isotopes in the tissue of a subject. The isotopes are typically administered to the subject by injection of probe molecules that comprise a positron-emitter isotope (radioisotopes, radionuclides), such as [18F], [11C], [13N], or [15O], which are attached to a molecule that is readily metabolized or localized in the subject, e.g., glucose, or that chemically binds to receptors within the subject. In some cases, the isotope can be administered to the subject as a solution or by inhalation.
Generally, radioisotopes are produced by bombarding a target material with a particle beam of a particle accelerator, e.g., a cyclotron. Thereafter, the radioisotopes are radiochemically processed into one or more radio-labeled molecular imaging probes for subsequent introduction into the subject. A number of devices for producing and automatically radiochemically synthesizing molecular imaging probes are known, for example, the Eclipse® line of cyclotrons and Explora® line of radiochemical-synthesizing devices and are known and are commercially available from Siemens Medical Solutions USA, Inc. of Malvern, Pa. Other examples of cyclotron, radiochemical synthesizing devices, e.g., gas processing units, and components therefor are described in U.S. Pat. Nos. 6,011,825 and 6,599,484 and U.S. Pat. Pub. Nos. 2002/0028177, 2005/0084055, 2006/0285623, and 2007/0043213, which disclosures are incorporated herein by reference.
An important factor in the production of radio-labeled molecular imaging probes is specific activity. Specific activity of a radioisotope or molecular imaging probe is the amount of radioactivity relative to the mass of the radioisotope or molecular imaging probe, and is often measured in Ci/μmol. The mass consists of all isotopic forms of the radioactive label. Accordingly, the specific activity can be affected by known synthesis processes, for example, the addition of stable isotopes during processing can result in dilution, or lowering of specific activity.
By way of example, in the case of 18F the maximum specific activity is 1,710 Ci/μmol. [18F] fluoride ion produced by proton bombardment of a metal target filled with [18O] water in a cyclotron typically has a specific activity of about 50-100 Ci/μmol, which represents up to a 40 to 1 dilution with stable [19F] that is present in the [18O] water and released from the metal target body and polymeric valves and tubing of the target delivery system. In general, [18F] labeled molecular imaging probes prepared from [18F] fluoride ion have a specific activity of about 2-5 Ci/μmol after coupling of the [18F] ion to a probe molecule, which illustrates that the radiochemical synthesis process results in another 25 to 1 dilution with stable [19F]. Fluoride ion delivered from the cyclotron target will typically contain 0.2-0.4 μg (10-20 μmol) stable [19F] fluoride ion along with the radioactive [18F] fluoride ion. If the activity delivered is 1.0 Ci, the [18F] fluoride ion mass will be about 9.0 ng or 0.5 nmol.
Similar issues arise when using [11C] and other radioactive isotopes because known radiochemical synthesis processes are primary sources of unwanted [12C] and other stable isotopes. For example, the maximum specific activity of [11C] is 9,240 Ci/μmol. However, one current method of producing [11C]CO is involves passing a volume of gas, e.g. [11C]CO2, over a packed bed of carbon and copper granules. As a result, the [12C] carbon granules of the packed bed act as a source of contamination of the [11C]CO and ultimately reduce the specific activity.
Accordingly, there is a need for a method and device for producing radio-labeled molecular imaging probes, and more specifically [11C]CO and [15O]CO, which exhibit higher specific activities while maintaining the simplicity and ease of current known devices and methods.
A method for reducing positron emitter isotope labeled CO2 to positron emitter isotope labeled CO generally comprises contacting a volume of the positron emitter isotope labeled CO2 with a metal oxide, such as Iron (II) oxide, to produce CO. In a preferred embodiment, the Iron (II) oxide is powdered and has a particle size of −10 mesh. In some embodiments, the CO2 comprises [11C] and a portion thereof is reduced to [11C]CO. In other embodiments, the CO2 comprises [15O] and a portion thereof is reduced to [15O]CO. In an embodiment, the CO2 is introduced into the reaction vessel, which is heated to a temperature between 900 and 1000° C., and more preferably, to a temperature between 925 and 975° C., and even more preferably, to a temperature of about 950° C. In an embodiment, the method further comprises removing un-reacted CO2 from the volume after the volume has contacted and substantially reacted with the Iron (II) oxide. In a preferred embodiment, removing of any un-reacted CO2 is accomplished by introducing the volume into a soda-lime trap. In an embodiment, the CO that is produced is delivered to a target, such as a storage vessel or subject.
A device for reducing positron emitter isotope labeled CO2 to positron emitter isotope labeled CO generally comprises a first heated reaction vessel comprising a metal oxide, such as Iron (II) oxide and a second reaction vessel comprising a CO2 removing agent wherein a first continuous fluid comprising the positron emitter isotope labeled. CO2 is introduced into the first heated reaction vessel to thereby reduce CO2 to CO via the Iron (II) oxide. A second continuous fluid comprising CO2 and CO is produced by the reaction is introduced into the second reaction vessel to remove any un-reacted CO2 to form a third continuous fluid, which substantially comprises CO. The third continuous fluid is delivered to a target, such as a storage vessel or subject. In some embodiments of the device, the CO2 comprises at least one of [11C]CO2 and [15O]CO2. In a preferred embodiment the first heated reaction vessel is heated to a temperature between 900 and 1000° C., and preferably, to a temperature between 925 and 975° C., and even more preferably, to a temperature of about 950° C. In a preferred embodiment, the Iron (II) oxide is in powder form and has a particle size of −10 mesh. In an embodiment, the CO2 removing agent comprises a soda-lime trap.
The invention will now be more fully described by way of example with reference to the accompanying drawings in which:
The present invention will now be described and disclosed in greater detail. It is to be understood, however, that the disclosed embodiments are merely exemplary of the invention and that the invention may be embodied in various and alternative forms. Therefore, specific structural and/or functional details disclosed herein are not to be interpreted as limiting the scope of the claims, but are merely provided as an example to teach one having ordinary skill in the art to make and use the invention.
Referring now to the figures,
Referring now to
By contrast, as shown in
As shown in the following tables, experiments comparing yield and saturation percentages of a target gas using the inventive Iron (II) Oxide packing, carbon and copper packing, molybdenum wire packing and molybdenum powder packings show that the Iron (II) Oxide packing, surprisingly and unexpectedly, exhibits substantially equivalent conversion and saturation yields as carbon/copper packings, which packings serve as the benchmark of commercially viable products. When compared with molybdenum wire and molybdenum powder packings, which are not deemed to be commercially viable, the Iron (II) Oxide packings show much greater conversion and saturation yields. The experiments were conducted using cyclotron DV-91 and a production Siemens GPU assembly (Model No: 3601001-00). CO2 gas was introduced into a heated furnace/reaction vessel containing the specifically identified packing configuration. The % conversions and saturation yields of CO were then determined from the reaction products.
Experimental Results:
It is thus seen that the use of an Iron (II) Oxide packing according to the invention to reduce [11C]CO2 or [15O]CO2 to CO results in the formation of a CO gas having an equivalent conversion and saturation yield when compared with CO produced using carbon and copper packings, but which inherently has a greater specific activity as the result of the removal of carbon in the reduction of CO2 to CO— all while maintaining the simplicity and ease of current known devices and methods. It will be recognized that although the invention has been described using Iron (II) oxide as a reactant, other metal oxides may be used as appropriate.
It should be appreciated by those having ordinary skill in the art that while the present invention has been illustrated and described in what is deemed to be the preferred embodiments, various changes and modifications may be made to the invention without departing from the spirit and scope of the invention. Therefore, it should be understood that the present invention is not limited to the particular embodiments disclosed herein.
| Number | Name | Date | Kind |
|---|---|---|---|
| 5859070 | Jackson et al. | Jan 1999 | A |
| 20050142055 | Miyake et al. | Jun 2005 | A1 |
| Number | Date | Country |
|---|---|---|
| 1 463 065 | Sep 2004 | EP |
| Number | Date | Country | |
|---|---|---|---|
| 20080286873 A1 | Nov 2008 | US |
