Patent Application
20050276751
1. Field of the Invention
The invention relates generally to the field of radiotracer synthesizers. More particularly, the invention relates to a system and a method for producing gallium-68 radiopharmaceutical agents.
2. Discussion of the Related Art
Positron emission tomography (PET) is an in vivo imaging method which uses gamma radiotracers to track the biochemical, molecular, and/or pathophysiological processes in humans and animals. In PET systems, positron-emitting isotopes serve as beacons for identifying the exact location of diseases and pathological processes under study without surgical exploration of the human body. With these non-invasive imaging methods, the diagnosis of diseases may be more comfortable for patients, as opposed to the more traditional and invasive approaches, such as exploratory surgeries.
Currently, some of the available radiotracers are produced from a cyclotron (F-18) process. A cyclotron system accelerates charged particles to high speeds and causes these charged particles to collide with a target to produce a nuclear reaction and subsequently create a radioisotope. However, the cyclotron-based tracers are constrained by the availability of local cyclotron and the cost of production.
Another method for producing radiotracers is through use of a generator process. The generator process uses a parent-daughter (P/D) nucleic pair where the parent (P) isotope decays to a short-lived daughter (D) isotope used for imaging. However, the current generator-based radiotracers are limited by the half-life of radioisotopes and the limited choices of imaging agents. For example, the copper-62 generator produces a Cu-62 based radioisotope with a half life of less than 10 minutes. As known in the art, radiosynthesis of radiotracers must be rapid because the usable amount of the radioisotope will decay with lengthy chemical synthesis and can cause a higher risk of radiation exposure during the production process.
The referenced shortcomings are not intended to be exhaustive, but rather are among many that tend to impair the effectiveness of previously known techniques concerning the production of radiotracers; however, those mentioned here are sufficient to demonstrate that the methodologies appearing in the art have not been satisfactory and that a significant need exists for the techniques described and claimed in this disclosure.
The present invention provides a system and method for producing an isotope with a prolonged half-life and producing both water and lipid soluble PET tracers in an efficient manner. Further, the invention produces an isotope that permits a more comprehensive radiochemistry for a variety of PET imaging agents.
In one respect, a method for producing a gallium-68 (Ga-68) radiopharmaceutical agent is provided. The method may include providing an admixture of Ga-68 and hydrochloric acid. The hydrochloric acid may subsequently be removed by an evaporation process in which the admixture may be heated to approximately 95-105° Celsius for approximately 10 to 15 minutes, yielding substantially purified Ga-68. In one embodiment of the invention, the admixture may be heated to approximately 100° Celsius.
The substantially purified Ga-68 may be mixed with a buffer and a prodrug to produce a Ga-68 radiopharmaceutical agent. In one embodiment of the invention, the buffer may be a sodium-acetate buffer. To facilitate the mixing of buffer and prodrug with the substantially purified Ga-68, nitrogen may be provided. In another embodiment, a carrier, for example, GaCl3 may also be provided to the substantially purified Ga-68 to produce the radiopharmaceutical agent.
In another respect, a system is provided. The system includes a generator, such as a Ga-68 generator which provides an admixture including Ga-68 and hydrochloric acid. The system may also include a heater for heating the admixture, which may be stored in a mixing chamber. The heater may heat the admixture to approximately 95-105° Celsius for approximately 10 to 15 minutes to induce the evaporation of the hydrochloric acid, leaving substantially purified Ga-68. In one embodiment, the heater heats the admixture to approximately 100° Celsius
The system may also include a valve assembly that may at least provide a buffer, for example, a sodium acetate buffer, a carrier, for example, GaCl3, and a prodrug to mix with the purified Ga-68 to produce a Ga-68 radiopharmaceutical agent. Nitrogen may be provided via a valve within the valve assembly to aid the mixing of the buffer, prodrug, and the purified Ga-68. In one embodiment, the mixing process may be captured by a camera coupled to the mixing chamber, where the camera may provide images from the mixing to a processor coupled to the camera to ensure quality control of the synthesis process.
The valve assembly and the heater may be operably controlled by a control system. The control system may receive instructions from a computer programmable software that may facilitate the operations of the system.
These, and other, embodiments of the invention will be better appreciated and understood when considered in conjunction with the following description and the accompanying drawings. It should be understood, however, that the following description, while indicating various embodiments of the invention and numerous specific details thereof, is given by way of illustration and not of limitation. Many substitutions, modifications, additions and/or rearrangements may be made within the scope of the invention without departing from the spirit thereof, and the invention includes all such substitutions, modifications, additions and/or rearrangements.
The drawings accompanying and forming part of this specification are included to depict certain aspects of the invention. A clearer conception of the invention, and of the components and operation of systems provided with the invention, will become more readily apparent by referring to the exemplary, and therefore nonlimiting, embodiments illustrated in the drawings, wherein like reference numerals (if they occur in more than one view) designate the same or similar elements. The invention may be better understood by reference to one or more of these drawings in combination with the description presented herein. It should be noted that the features illustrated in the drawings are not necessarily drawn to scale.
The invention and the various features and advantageous details thereof are explained more fully with reference to the nonlimiting embodiments that are illustrated in the accompanying drawings and detailed in the following description. It should be understood that the detailed description and the specific examples, while indicating specific embodiments of the invention, are given by way of illustration only and not by way of limitation. Various substitutions, modifications, additions and/or rearrangements within the spirit and/or scope of the underlying inventive concept will become apparent to those of ordinary skill in the art from this disclosure.
The present invention includes a system and a method for the synthesis of gallium-68 (Ga-68) radiopharmaceutical agents used in imaging methods, such as Positron Emission Tomography (PET) imaging. The use of Ga-68 may permit a more comprehensive radiochemistry due to the 68-minute half-life of Ga-68. Further, the system and method of the present invention may be capable of producing water and lipid PET tracers with at least a 95% yield, if not 100% yield, at an efficient rate, e.g. less than 20 minutes.
Referring to
System 100 may also include a plurality of inputs 112, 114, and 116. Each input may provide the system 100 with chemical compounds, drugs, and/or other components needed to produce a radiopharmaceutical agent. For example, input 112 may provide nitrogen (N2) to aid in the transfer and/or mixing of the chemical compounds, drugs, and/or other products through the system 100. Input 114 may provide a vacuum pump which may be used to create a vacuum in one of the chambers, such as a mixing chamber of the system. Input 116 may provide a prodrug to the system to produce the radiopharmaceutical agent. System 100 may include at least one output, such as a Ga-68 radiopharmaceutical agent. The functionality of each of the components of system 100 will further be discussed below.
Coupled to system 100 may be a control system 120, which may include a computing device 135, a program storage media 130, and a controller 125, as shown in
The synthesis process begins with the production of Ga-68 from the generator 108. During the synthesis, an acid, such as hydrochloric acid, may be added to produce the Ga-68. Due to the harmful effects of the hydrochloric acid to a patient, there is a need to remove the hydrochloric acid before producing the radiopharmaceutical agent.
The valves in the valve assembly may be controlled by controller 120 to be “ON” position providing an input or transferring a product, or an “OFF” position where no transfer through the system occurs at that valve. In one embodiment, the generator 108 may provide an admixture which may comprise Ga-68 and hydrochloric acid. The admixture may be routed to the mixing chamber 200 (V2, V2, V4, and V5 “ON”). In addition, a vent 202 may be utilized (V6 “ON”). To ensure a sterile condition and no aqueous back flow to the generator 108, after the transfer of the admixture to the mixing chamber 200, V4, V3, V2 and V1 may be switched to an “OFF” position.
Next, acetonitrile may be added to the admixture in the mixing chamber 200 for an azeotropic evaporation of the hydrochloric acid. The heater 110, which may be coupled to the mixing chamber 200, may be turned on to approximately 95-105° Celsius, under vacuum (V6 “ON”) and nitrogen (V7, V8, V9, and V11 “ON”) to begin the removal of the hydrochloric acid from the admixture. The heater remains on for approximately 10-15 minutes to ensure the complete evaporation of the hydrochloric acid leaving substantially purified Ga-68 in the mixing chamber 200. After the evaporation, the mixing chamber 200 may be cooled down by adding nitrogen for approximately 30 seconds (heater 110 “OFF”; V7, V8, V9 and V11 “ON”).
To form the Ga-68 radiopharmaceutical agent, a buffer, such as a sodium acetate buffer, a carrier, and a prodrug may be added to the mixing chamber 200 (V9 “OFF”, VS and V12 “ON”). In one embodiment, the carrier may be cold or un-labeled gallium-chloride (GaCl3) at a specific molar concentration, such as 4 mM. The substantially purified Ga-68, buffer, carrier, and prodrug may be stirred by providing nitrogen to the mixing chamber 200 (V5 “OFF” and V9 “ON”). The Ga-68 radiopharmaceutical agent may be subsequently transferred and stored in a sterile container, such as the collection chamber 208 (V6 and V7 “OFF”; V5, V4, V8, and V9 “ON”; and V10 and VII “ON”). The collection chamber 208 may be made of lead and may include a door (not shown) to provide access to the product stored within the collection chamber 208.
Once the product is transferred and stored in the collection chamber 208, water, a carrier, such as GaCl3, or transchelator may be added (V4 and V9 “OFF”; V5 and V6 to the vent “ON”) to the mixing chamber and may be subsequently transferred to the collection chamber 208 to optimize the yield of the radiopharmaceutical agent (V6 “OFF”; V5, V4, and V9 “ON”).
The operation of system 100 may be controlled by control system 120 (
Referring to
Software window 300 may also display control 310 which is temperature gauge that monitors the heat emitted from the heater as well as allow the setting of a heater to a desired temperature, e.g., 100° Celsius. In addition, the software program may also provide a more detailed analysis of the heater as illustrated in
In one embodiment of the invention, the software may provide a display window for configuring system 100. Referring to
In another embodiment of the invention, a method may be provided for producing a radiopharmaceutical agent. Referring to
Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made to the embodiments herein without departing from the spirit and scope of the invention as defined by the appended claims. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, and composition of matter, means, methods and steps described in the specification. As one of ordinary skill in the art will readily appreciate from the disclosure of the present invention, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present invention. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.
This patent application claims priority to, and incorporates by reference in its entirety, U.S. provisional patent application Ser. No. 60/538,191 filed on Jan. 20, 2004.
| Number | Date | Country | |
|---|---|---|---|
| 60538191 | Jan 2004 | US |
