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    • 专利摘要:
    RADIOPHARMACEUTICAL MICROFLUID SYNTHESIS SYSTEM, METHOD FOR PRODUCING AN AMOUNT OF RADIOPHARMACEUTICALS AND SYNTHESIZING A RADIOCHEMIST, SYSTEM FOR SYNTHESING A RADIOPHARMACEUTICALS AND CONDUCTING AUTOMATED QUALITY CONTROL TESTS OF A RADIOPHARMACEUTICAL CONTROL DEVICE ON A CONDUCTING DEVICE. A system for producing radiopharmaceutical microfluids and a process for synthesizing by running approximately one (1) to four (4) unit doses of a radiopharmaceutical biomarker for use in positron emission tomography (PET) is described. The system includes a reaction vessel that receives a radioisotope from an accelerator or other radioisotope generator from an accelerator or other radioisotope generator. Aqueous and organic reagents are introduced into the reaction vessel, and the mixture is heated to synthesize a solution of a preselected radiopharmaceutical. The radiopharmaceutical solution is passed through a solid extraction column and filter for purification. The synthesis process reduces waste and allows for production. The synthesis process reduces waste and allows the production of radiopharmaceuticals as needed. The synthesis process allows production in the place and close to the place where the unit dose will be administered to the patient, which reduces (...).
    公开号:BR112012006679B1
    申请号:R112012006679-0
    申请日:2010-09-21
    公开日:2021-04-20
    发明作者:Ronald Nutt；Anthony M. Giamis；Aaron McFARLAND
    申请人:Best Abt, Inc.；
    IPC主号:
    专利说明:

    CROSS REFERENCE FOR RELATED ORDERS
    [001] Not applicable. STATEMENT REGARDING RESEARCH or DEVELOPMENT SPONSORED BY THE FEDERAL GOVERNMENT
    [002] Not applicable. BACKGROUND OF THE INVENTION 1. Field of invention
    [003] This invention relates to an apparatus and a chemical process to synthesize and purify radiopharmaceuticals for use in positron emission tomography (PET). Specifically, the present invention relates to a system for analyzing a liquid PET biomarker sample. 2. Description of the state of the art
    [004] A biomarker is used to question a biological system and can be created by "labeling" and labeling certain molecules, including biomolecules, with a radioisotope. A biomarker that includes a positron emission radioisotope is required for positron emission tomography (PET), a non-invasive diagnostic imaging procedure that is used to assess biochemical and functional metabolic or perfusion activity in different systems of organs of the human body. Because PET is a very sensitive biochemical imaging technology and the first disease precursors are mainly biochemical in nature, PET can detect many diseases before anatomical transformations occur and often before medical symptoms become if apparent. PET is similar to other nuclear medicine technologies in that a radiopharmaceutical is injected into a patient to assess metabolic activity in one or more regions of the body. However, PET provides information not available from traditional imaging technologies, such as magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound, which capture the image of the patient's anatomy rather than capturing physiological images. . Physiological activity provides a much earlier measure of detection for certain forms of disease, cancer in particular, than anatomical changes over time.
    [005] A positron-emitting radioisotope undergoes radioactive decay, whereby its nucleus emits positrons. In human tissue, a positron inevitably travels less than a few millimeters before interacting with an electron, converting the total mass of the positron and electron into two photons of energy. Photons are displaced approximately 180 degrees from each other and can be detected simultaneously as “coincident” photons on opposite sides of the human body. The modern PET scanner detects one or both photons, and the computerized reconstruction of the acquired data allows a visual representation of the distribution of the isotope and, consequently, of the labeled molecule within the organ being visualized.
    [006] The most clinically important positron-emitting radioisotopes are produced by a cyclotron. Cyclotrons work by accelerating electrically charged particles along quasi-spherical orbits to a predetermined extraction energy, usually on the order of millions of electron volts. The high-energy electrically charged particles form a continuous beam that travels along a predetermined path and bombards a target. When the bombarded particles interact with the target, a nuclear reaction takes place at a subatomic level, resulting in the production of a radioisotope. The radioisotope is then chemically combined with other materials to synthesize a radiochemical or radiopharmaceutical (hereinafter “radiopharmaceutical”) suitable for introduction into the human body. Cyclotrons traditionally used to produce radioisotopes for use in PET have been large machines that require a great deal of space and radiation shielding. These requirements, together with cost considerations, make it unfeasible for private hospitals and imaging centers to have on-site facilities for the production of radiopharmaceuticals for use in PET.
    [007] Thus, in current standard practice, radiopharmaceuticals for use in PET are synthesized in centralized production facilities. Radiopharmaceuticals, then, must be transported to hospitals and imaging centers up to 200 miles away. Due to the relatively short half-life of the handful of clinically important positron-emitting radioisotopes, it is expected that a large portion of the radioisotopes in a given transfer will decay and cease to be useful during the transport phase. To ensure that a sufficiently large sample of active radiopharmaceutical is present at the time of application to a patient in a PET procedure, a much larger amount of radiopharmaceutical must be synthesized prior to transport. This involves the production of radioisotopes and the synthesis of radiopharmaceuticals in quantities much greater than one (1) unit dose, with the expectation that many of the active atoms will decay during transport.
    [008] The need to transport radiopharmaceuticals from the production facility to the hospital or imaging center (hereinafter “treatment site”) also dictates the identity of isotopes selected for PET procedures. Currently, fluorine isotopes, and especially fluor-18 (or F-18), enjoy more widespread use. The F-18 radioisotope is commonly synthesized in [18F]fluorodeoxyglucose, or [18F]FDG, for use in PET. F-18 is widely used mainly because of its half-life, which is approximately 110 minutes, which allows enough time to transport a useful amount. The current system of centralized production and distribution largely prohibits the use of other potential radioisotopes. In particular, carbon-11 has been used for PET, but its relatively short half-life of 20.5 minutes makes its use difficult if the radiopharmaceutical is to be transported any considerable distance. Similar considerations largely govern the use of nitrogen-13 (half-life: 10 minutes) and oxygen-15 (half-life: 2.5 minutes).
    [009] As with any medical application involving the use of radioactive materials, quality control is important in the synthesis and use of PET radiopharmaceutical biomarkers, both to safeguard the patient and to ensure the efficacy of the administered radiopharmaceutical. For example, for the synthesis of [18F]FDG from mannose triflate, there are several quality control tests. The final product of [18F]FDG should be a clear, clean solution, free from impurity particles; however, it is important to test the color and clarity of the final radiopharmaceutical solution. The final radiopharmaceutical solution is usually filtered through a sterile filter prior to administration, and it is advisable to test the integrity of this filter after the synthesized radiopharmaceutical solution has passed through it. The acidity of the final radiopharmaceutical solution should be within acceptable limits (largely a pH between 4.5 and 7.5 for [18F]FDG, although this range may differ depending on the application and the radiopharmaceutical indicator involved). The final radiopharmaceutical solution must be tested for the presence and levels of volatile organics, such as ethanol or methyl cyanide, that may remain from the synthesis process. Likewise, the solution must be tested for the presence of crown ethers or other reagents used in the synthesis process, as the presence of these reagents in the final dose is problematic. In addition, the radiochemical purity of the final solution must be tested to ensure that it is high enough for the solution to be useful. Other tests, such as radionuclide purity tests, tests for the presence of bacterial endotoxins and synthesis system sterility tests are known in the prior art.
    [0010] Currently, most or all of these tests are performed on each batch of radiopharmaceuticals, which will contain several doses. Quality control tests are performed separately by human technicians, and completing all these tests typically takes between 45 and 60 minutes. BRIEF SUMMARY OF THE INVENTION
    [0011] In the present invention, a PET biomarker production system includes a radioisotope generator, a radiopharmaceutical production module and a quality control module. The PET biomarker production system is designed to produce approximately one (1) unit dose of a radiopharmaceutical biomarker very efficiently. The general setup includes a small particle accelerator, low power cyclotron, or other radioisotope generator (hereinafter “accelerator”) to produce approximately one (1) unit dose of a radioisotope. The system also includes a microfluidic chemical production module. The chemical production module or CPM receives the unit dose of radioisotope and reagents to synthesize the unit dose of a radiopharmaceutical.
    [0012] The accelerator produces per run a maximum amount of radioisotope that is approximately equal to the amount of radioisotope required by the microfluidic chemical production module to synthesize a unit dose of biomarker. Chemical synthesis using microreactors or microfluidic chips (or both) is significantly more efficient than chemical synthesis using conventional technology (macroscale) Percentage results are higher and reaction times are shorter, thus significantly reducing the amount of radioisotope required to synthesize a unit dose of radiopharmaceutical. In this sense, because the accelerator serves to produce per run only relatively small amounts of radioisotope, the maximum power of the beam generated by the accelerator is approximately two to three orders of magnitude smaller than that of a conventional particle accelerator. As a direct result of this dramatic reduction in maximum beam power, the accelerator is significantly smaller and lighter than a conventional particle accelerator, has fewer stringent infrastructure requirements, and requires much less electricity. Additionally, many of the low-power small throttle components are less expensive than comparable components of conventional throttles. Therefore, it is possible to use the low power accelerator and follow-up CPM [MPQ] within the treatment site.
    [0013] Because there is no need for radiopharmaceuticals to be synthesized in a central location and then transported to distant treatment sites, fewer radiopharmaceuticals need to be produced, and different isotopes, such as carbon 11, can be used if desired.
    [0014] If the accelerator and COM [MPQ] are in the hospital basement or simply across the street from the imaging center, then PET radiopharmaceuticals can be administered to patients almost immediately after synthesis. However, eliminating or significantly reducing the transport phase does not eliminate the need to perform quality control tests on the CPM [MPQ] and the resulting radiopharmaceutical solution itself. In addition, it is essential to reduce the time required to perform these quality control tests in order to take advantage of the reduced time between synthesis and administration. The traditional 45 to 60 minutes required for quality control tests on macroscale-produced radiopharmaceuticals are clearly inadequate. In addition, since the accelerator and CPM [MPQ] are producing a radiopharmaceutical solution that is approximately only one (1) unit dose, it is important that quality control testing does not use too much of the radiopharmaceutical solution; after some solution has been withdrawn for testing, sufficient radiopharmaceutical solution must remain to produce an effective unit dose.
    [0015] The sample card and quality control module allow the operator to conduct quality control tests in reduced time using microscale test samples from the radiopharmaceutical solution. The sample card works in conjunction with the CPM [MPQ] to collect sample radiopharmaceutical solution at the scale of up to 100 microliters per sample. The sample card then interacts with the quality control module (or QCM) to deliver the samples to multiple test vessels, where the samples go through several automatic diagnostic tests. Because quality control tests are automated and run in parallel on smaller samples, the quality control testing process can be completed in 20 minutes. Also, under the traditional microscale radiopharmaceutical synthesis system and quality control test, a radiopharmaceutical solution would be produced with one batch, and quality control tests would be performed on the entire batch, with each batch producing multiple doses of radiopharmaceutical. Here, because the PET biomarker production system produces approximately one unit dose per run, at least some quality control tests can be performed on each dose rather than the batch as a whole. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
    [0016] The aforementioned features of the invention will be more clearly understood from the following detailed description of the invention read in conjunction with the drawings, in which:
    [0017] Figure 1 is a schematic illustration of an embodiment of the biomarker production system for PET in general, including the accelerator, the chemical production module (CPM) [MPQ], the dose synthesis card, the sample and quality control module (QCM);
    [0018] Figure 2 is another view of the embodiment shown in Figure 1, showing the sample card interacting with the quality control module (QCM);
    [0019] Figure 3 is a flow diagram of an embodiment of a chemical production module (CPM) [MPQ], the dose synthesis card and the sample card;
    [0020] Figure 4 is a flow diagram of an embodiment of the sample card interacting with an embodiment of the quality control module (QCM); and
    [0021] Figure 5 is a schematic illustration of an embodiment of the dose synthesis card and the sample card. DETAILED DESCRIPTION OF THE INVENTION
    [0022] A chemical production module and dose synthesis card for a radiopharmaceutical biomarker production system for PET are described more fully below. This invention can, however, be embodied in many different ways and should not be construed as limited to the embodiments set out herein. Rather, these embodiments are provided to ensure that this disclosure is exhaustive and complete, and to ensure that it fully conveys the scope of the invention to those skilled in the art.
    [0023] The chemical production module, dose synthesis card and sample card work together with a complete biomarker production system for PET. As shown in Figure 1, one embodiment of such a biomarker production system for PET comprises an accelerator 10, which produces the radioisotopes; a chemical production module (or CPM [MPQ]) 20; a 30 dose synthesis card; a sample card 40; and a quality control (or QCM) module 50. Once accelerator 10 has produced a radioisotope, the radioisotope travels through a radioisotope delivery tube 112 to the dose synthesis card 30 attached to the CPM 20. The CPM 20 contains reagents and solvents that are needed during the radiopharmaceutical synthesis process. In the dose synthesis card 30, the radiopharmaceutical solution is synthesized from the radioisotope and then purified for testing and administration. Following synthesis and purification, a small percentage of the resulting radiopharmaceutical solution is diverted to sample card 40, while the remainder flows into a 200 dose container. radiopharmaceutical solution has flowed into sample card 40, an operator removes sample card 40 from the CPM 20 and connects it to the QCM 50, where various diagnostic instruments perform automated quality control tests on the samples.
    [0024] Figures 3 and 4 present a more detailed overview of the processes of complete synthesis and quality control testing for an embodiment of the present invention. In this embodiment, the radioisotope involved is fluor-18 (F-18), produced from bombardment in a heavy water cyclotron containing the oxygen-18 isotope. However, the sample card and quality control module also work with radiopharmaceutical synthesis systems using other isotopes, including carbon-11, nitrogen-13 and oxygen-15.
    [0025] As shown in Figure 3, the radioisotope enters a reaction chamber or reaction vessel 110 from the radioisotope delivery tube 112. At this stage, the F-18 radioisotope is further mixed with heavy water quantities from the generator. biomarker. Then, a first organic ingredient is introduced into reaction vessel 110 from a reagent storage compartment 120 by an organic inlet pump 124. In some embodiments, the first organic ingredient includes a solution of α1,10-complexed potassium. diaza-4,7,13,16,21,24-hexoxabicyclo[8.8.8]hexacosane (commonly called Kryptofix 222™, hereinafter “kryptofix”) or a similar crown ether. In some embodiments, the potassium kryptofix complex or similar organometallic complex is carried by acetonitrile as a solvent. Potassium activates the F-18 fluoride radioisotope, while kryptofix binds potassium atoms and inhibits the formation of a potassium fluoride complex. Next, a gas inlet 142 fills reaction vessel 110 with an inert gas, such as dry nitrogen, the gas having been stored in a storage area 140 within or near the CPM [MPQ] 20. in reaction vessel 110 is heated by nearby heating source 114 to remove residual heavy water by evaporation of the azeotropic water/acetonitrile mixture. A rarefaction 150 helps to remove vaporized water. Then, organic inlet pump 124 adds a second organic ingredient from a second reagent storage compartment 122 to the mixture in reaction vessel 110. In many embodiments, the second organic ingredient is mannose triflate in dry acetonitrile. The solution is then heated to approximately 110°C for approximately two minutes. At this point, F-18 has bound to mannose to form the immediate precursor to [18F]FDG, commonly 18F-fluorodeoxyglucose tetraacetate (FTAG). Next, aqueous acid - in many embodiments, aqueous hydrochloric acid - is introduced from storage compartment 130 via an aqueous inlet pump 132. The hydrochloric acid removes the protective acetyl groups on the 18F-FTAG, leaving the 18F-fluorodeoxyglucose (i.e., [18F]FDG).
    [0026] The [18F]FDG that has been synthesized must be purified prior to testing and administration. [18F]FDG in solution passes from reaction vessel 110 through a solid phase extraction column 160. In some embodiments of the present invention, the solid phase extraction column 160 comprises an extension filled with an ion exchange resin, a alumina-filled span and a carbon-18-filled span. The [18F]FDG then passes through a filter 170, which, in many embodiments, includes a Millipore filter with pores approximately 0.22 micrometers in diameter.
    [0027] Once the radiopharmaceutical solution has passed through filter 170, part of the solution is diverted to sample card 40, which contains a quantity of sample containers 402a-e., which, in some embodiments, hold approximately 10 microliters of the solution. The number of sample containers will vary according to the number of quality control tests to be performed for that run, and the system is adapted to work with different sample cards containing varying amounts of sample containers. The remainder of the radiopharmaceutical solution (ie, all of the solution that is not diverted for quality control testing) flows into dose container 200, ready for administration to a patient.
    [0028] Once the samples are in the sample containers 402a-e of the sample card 40, an operator inserts the sample card 40 into the QCM 50, as shown in Figure 2. As shown in Figure 4, the radiopharmaceutical samples travel from sample containers 402a-e into test containers 502, 602, 702, 802 and 902 within QCM 50. Within QCM 50, there are instruments to perform a number of automated quality control tests for each run of radiopharmaceutical produced by the radiopharmaceutical synthesis system.
    [0029] To test color and clarity, a light source 504 shines white light through the sample in test container 502. An electronic eye 506 then detects the light that has passed through the sample and measures that light intensity and color against reference samples.
    [0030] To test the acidity of the radiopharmaceutical solution, the 604 pH tester, ie pH probe or color strip, measures the pH of the sample in the 602 sample container.
    [0031] To test for the presence of volatile organics, a heat source 704 heats the sample in sample container 702 to approximately 150 degrees Celsius so that the aqueous sample compounds, now in the form of a gas, enter an adjacent chromatograph 706. A 708 gas sensor microarray (informally, an “electronic nose”) then detects the presence and prevalence (eg, as ppm) of such chemicals as methyl cyanide and ethanol.
    [0032] To test for the presence of kryptofix, the sample in test container 802 is placed on an 804 gel comprising silica gel with iodoplatinate. The sample and gel 804 are then heated, and a color recognition sensor 806 measures the resulting color of the sample with a yellow color indicating the presence of kryptofix.
    [0033] To test the radiochemical purity of the sample, the sample in test vessel 902 is eluted through a 904 silica column using a carrier mixture of acetonitrile and water. In some embodiments, acetonitrile and water are mixed in a 9:1 ratio. A 906 radiation probe measures the activity of the solution as it is eluted. As [18F]FDG has an elution time that can be accurately predicted, the 906 probe measures the percentage of activity that elutes at or close to the predicted elution time for [18F]FDG. A percent of 95% or greater indicates acceptable radiochemical purity.
    [0034] In addition, a filter integrity test is also performed for each dose that is produced. As shown in Figure 3, after the radiopharmaceutical solution has passed filter 170, the integrity of filter 170 is tested by passing inert gas from inert gas inlet 142 through filter 170 at increased pressure. A pressure sensor 302 measures the pressure of inert gas over filter 170 and detects whether filter 170 is still intact. Filter 170 must be capable of maintaining integrity under pressures of at least 50 pounds per square inch (psi).
    [0035] Figure 5 presents a schematic view of an embodiment of the dose synthesis card 30' together with the attached sample card 40'. The 30' dose synthesis card includes a reaction vessel 110a in which the radiopharmaceutical solution is synthesized. A radioisotope input 112a introduces radioisotope F-18 into reaction vessel 110a through a radioisotope input channel 1121. At this stage, the radioisotope is further mixed with heavy amounts of water from the biomarker generator. Then, an organic inlet 124a introduces a solution of potassium kryptofix complex in acetonitrile into the reaction vessel 110a through an organic inlet channel 1241. A combination of nitrogen and vacuum inlet 154 pumps nitrogen gas into the reaction vessel 110a through a gas channel 1540a and a valve 1541, which valve is currently in the open position. Mixture A in reaction vessel 110a is heated under a nitrogen atmosphere to azeotropically remove water from mixture A, the vaporized water being evacuated through gas channel 1540a and vacuum 154. Organic inlet 124a then introduces triflate. mannose in dry acetonitrile into reaction vessel 110a through organic inlet channel 1241. The solution is heated to approximately 110 degrees Celsius for approximately two minutes. At this stage, F-18 has bound to mannose to form an immediate precursor to [18F]FDG, FTAG. Next, aqueous hydrochloric acid is introduced into reaction vessel 110a through an aqueous inlet 132a and 20 of an aqueous channel 1321. The hydrochloric acid removes the protecting acetyl groups on the 18F-FTAG, leaving the 18F-fluorodeoxyglucose (i.e. [18F]FDG).
    [0036] Having been synthesized, the [18F]FDG in solution passes from the reaction vessel 110a through a post-reaction channel 1101 into a solid phase extraction column 160a, where some undesirable substances are removed from the solution, thus clearing the radiopharmaceutical solution. In some embodiments of the present invention, solid phase extraction (SPE) column 160a comprises an extension with an ion exchange resin, an extension filled with alumina, and an extension filled with carbon-18. The radiopharmaceutical passes through the SPE 160a column with a mobile phase that, in various embodiments, includes acetonitrile from organic inlet 124a. As some of the mobile phases and impurities emerge from the SPE column 160a, they pass through a second post-reaction channel 1542 and through a three-way valve 175 and overflow channel 1104 to an overflow receptacle 210. As the clarified radiopharmaceutical solution emerges from the SPE 160a column, the radiopharmaceutical solution then passes through a second post-reaction channel 1542 and through three-way valve 175 into a filter channel 1103 and, then through a 170a filter. Filter 170a removes other impurities (including particulate impurities), thus further clarifying the radiopharmaceutical solution. In many embodiments, filter 170a includes a Millipore filter with pores approximately 0.22 micrometers in diameter.
    [0037] Once the radiopharmaceutical solution has passed filter 170a, the clarified radiopharmaceutical solution travels through post-clarification channel 1105 into a sterile dose delivery container 200a, which, in the illustrated embodiment, is incorporated within a syringe 202. In some embodiments, the dose delivery container is pre-filled with a mixture of phosphate buffer and saline. As the clarified radiopharmaceutical solution fills the sterile dose administration container 200a, part of the solution B is dispersed through an extraction channel 1401, an open valve 1403 and a transfer channel 1402 into the 40’ card. The 40’ sample card contains a number of 404a-h sample loops, which hold separate aliquots of solution for upcoming testing, and a number of 408a-h valves, which, at this stage, are closed. Once the radiopharmaceutical test sample aliquots are collected, the 40' sample card is separated from the 30' dose synthesis card and inserted into the QCM, as shown in Figures 2 and 4. The aliquots then , travel through now open valves 408a-h to sample outlet ports 406a-h, from which aliquots pass into test containers, as shown in Figure 4. In some embodiments, each of the sample loops 404a-h holds approximately 10 microliters of sample solution. The number of sample loops will vary according to the number of QA tests to be performed for that run, and the system is adapted to work with different sample cards containing varying numbers of sample loops. After the sample aliquots pass into the sample card 40', any excess solution remaining in the dose delivery container 200a is withdrawn by a vent 156 through a first vent channel 1560b and thereafter conveyed through an open valve 1561 and through a second vent channel 1560a into overflow receptacle 210. Vacuum 154 evacuates residual solution from transfer channel 1402 through a now open valve 1403 and a solution evacuation channel 1540b.
    [0038] In some embodiments of the present invention, the CPM [MPQ] 20 contains sufficient amounts of reagents and solvents that are required during the radiopharmaceutical synthesis process to perform multiple runs without refill. In fact, in some embodiments, CPM [MPQ] 20 is loaded with enough reagents and solvents to produce several tens or even several hundred doses of radiopharmaceutical. Since reagents and solvents are stored in CPM [MPQ] 20, it is easier than under previous systems to keep reagents and solvents sterile and uncontaminated. In some embodiments, a sterile environment is supported and contamination inhibited by disposing of each dose synthesis card 30 and sample card 40 after a run; these system components are adapted to be disposable.
    [0039] Thus, each batch of reagents and solvents, periodically loaded into the CPM [MPQ] 20, will provide a batch of multiple doses of radiopharmaceutical, each dose produced in a separate run. Some quality control tests are performed for each dose that is produced, while other quality control tests are performed for each batch of doses. For example, in one embodiment of the present invention, the filter integrity test, the color and clarity test, the acidity test, the volatile organic substances test, the chemical purity test, and the radiochemical purity test are performed for each dose. On the other hand, some quality control tests only need to be run once or twice per batch, such as the radionuclide purity test (using a radiation probe to measure the half-life of F-18 in [ 18F]FDG), the bacterial endotoxin test and the sterility test. These tests are generally performed on the first and last doses of each batch. Because these batch quality control tests are performed less frequently, they may not be included in QCM, but may be performed by technicians using separate laboratory equipment.
    [0040] While the present invention has been illustrated by describing an embodiment, and while the illustrative embodiment has been described in detail, it is not Applicant's intention to restrict or in any way limit the scope of the claims appended to these details. Additional modifications will readily appear to those skilled in the art. The invention, in its broadest aspects, therefore, is not limited to specific details, representative apparatus and methods, and to the illustrative examples shown and described. Therefore, departures can be made from such details without abandoning the spirit and scope of the applicant's general inventive concept.
    权利要求:
    Claims (4)
    [0001]
    1. SYSTEM FOR SYNTHESIS OF A MICROFLUID RADIOPHARMACEUTICAL, characterized in that it comprises: a reaction vessel adapted to receive a radioisotope and at least one reagent, said reaction vessel being in heat transfer communication with a heat source, through which when said radioisotope and said at least one reagent are mixed in said reaction vessel and heat is applied to said reaction vessel from the heat source, a radiopharmaceutical solution is synthesized; a solid phase extraction column adapted to purify said radiopharmaceutical solution; a filter adapted to sterilize said radiopharmaceutical solution; and a container adapted to receive said radiopharmaceutical solution following its passage through said solid phase extraction column and said filter, said container holding an amount of purified radiopharmaceutical solution equal to, but not less than, one (1) unit dose of radiopharmaceutical; wherein said reaction vessel, said solid phase extraction column and said filter are incorporated into the disposable plate, said plate being discarded after one (1) run, and wherein said system is scaled to produce, per run, an amount of purified radiopharmaceutical solution equal to, but not less than, one (1) unit dose of the radiopharmaceutical.
    [0002]
    A SYSTEM according to claim 1, further comprising a plate sample adapted to receive multiple aliquots of said purified radiopharmaceutical solution to then test said passage of the purified radiopharmaceutical solution through said solid phase extraction column and of said filter.
    [0003]
    3. SYSTEM according to claim 1, characterized in that said radioisotope is selected from the group consisting of carbon-11, nitrogen-13, oxygen-15 and fluorine-18.
    [0004]
    4. SYSTEM according to claim 1, characterized in that said radiopharmaceutical is [18F]-2-fluoro-2-deoxy-D-glucose.
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    法律状态:
    2017-04-04| B11A| Dismissal acc. art.33 of ipl - examination not requested within 36 months of filing|
    2017-06-06| B04C| Request for examination: application reinstated [chapter 4.3 patent gazette]|
    2018-01-23| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|
    2018-04-10| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-01-02| B07G| Grant request does not fulfill article 229-c lpi (prior consent of anvisa) [chapter 7.7 patent gazette]|Free format text: NOTIFICACAO DE DEVOLUCAO DO PEDIDO POR NAO SE ENQUADRAR NO ART. 229-C DA LPI. |
    2019-07-16| B07A| Technical examination (opinion): publication of technical examination (opinion) [chapter 7.1 patent gazette]|
    2020-01-28| B25A| Requested transfer of rights approved|Owner name: ABT MOLECULAR IMAGING, INC. (US) |
    2020-02-18| B25A| Requested transfer of rights approved|Owner name: BEST ABT, INC. (US) |
    2020-11-03| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|
    2021-02-09| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-04-20| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 21/09/2010, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME MEDIDA CAUTELAR DE 07/04/2021 - ADI 5.529/DF |
    优先权:
    申请号 | 申请日 | 专利标题
    US12/565,544|2009-09-23|
    US12/565,544|US8333952B2|2009-09-23|2009-09-23|Dose synthesis module for biomarker generator system|
    PCT/US2010/002577|WO2011037615A1|2009-09-23|2010-09-21|Chemical production module and dose synthesis card for pet biomarker production system|
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