JP5380201B2 - Labeled compound supply system - Google Patents

Description

  The present invention relates to the production (synthesis) and supply of O-15 labeled gas used for O-15 gas-PET inspection using positron emission tomography (PET).

Quantitative image evaluation of cerebral blood flow, cerebral oxygen metabolism, and cerebral oxygen uptake rate using O-15-labeled compound (drug) by PET examination using positron emission tomography is possible, and the brain represented by cerebral infarction It is used for diagnosis of ischemic disease. In the medical treatment of stroke, it became clear that accurate treatment within 3 hours after the onset greatly affects the subsequent medical condition, and brain oxygen metabolism after onset, which is the most important information for knowing the ischemic state of brain tissue It is important to grasp quickly and accurately. The PET test is the only test that can accurately monitor cerebral oxygen metabolism by supplying O-15-labeled compounds (C ¹⁵ O, ¹⁵ O ₂ and H ₂ ¹⁵ O (or C ¹⁵ O ₂ )) to the subject. is there. However, since the time required for the test is as long as about 1.5 hours, physical and mental stress due to long-term restraint is great not only for the acute phase but also for the chronic phase subject, and its spread has been hindered. Today, as an aging society is screaming for the improvement of acute stroke medical care, the time required for PET testing is being reduced.

In the routine O-15 labeled gas-PET test, each of the three types of radiolabeled gases C ¹⁵ O, ¹⁵ O ₂ and C ¹⁵ O ₂ is administered to the subject continuously, and the radioactivity in the brain is increased. Collect PET imaging data in equilibrium. In this method, one labeled compound is synthesized and inhaled by the subject, and PET imaging is performed in a state where the distribution of radioactivity concentration in the body is in an equilibrium state, and then waiting for the decay of the radioactivity remaining in the body. Begin synthesis and inhalation of the next labeled compound. Here, when the gas used immediately before remains, the gas inhaled by the subject is a mixture of the gas supplied immediately before, which affects the test result. Further, impurities may be mixed in due to deterioration of the performance of the synthesis apparatus. To prevent this, a pre-inhalation test (pre-test) is required, which is also prescribed in the guidelines for PET drugs. In conventional drug delivery systems for supplying labeled compounds, O-15 labeled compounds are synthesized using O-15 generated in a cyclotron target box and the quality is confirmed through a quality checker. Was later provided to the subject. In the steady-state method, three times of PET imaging for three types of labeled compounds are performed. Since there is a waiting time for attenuation of radioactivity concentration during PET imaging, the quality of the synthesized labeled compounds is preliminarily determined in the drug supply system. After confirming, there was time to start inhalation.

In order to shorten the time for O-15 labeled gas-PET inspection, O-15 labeled gas-PET rapid inspection method (dual autoradiography method) has been developed that can complete the inspection within 20 minutes in total (International Publication 2006- 043674). Rapid testing is based on the finding that the temporal resolution of imaging is much shorter than previously thought, so that repeated administration of two labeled compounds without complete loss of radioactivity, A plurality of functions can be obtained as an image even with one imaging. In the rapid test method, the data collection procedure when administering _two labeled compounds ¹⁵ O ₂ and C ¹⁵ O ₂ is significantly different from the routine method. Any labeled compound is stopped for a short time before the brain radioactivity becomes balanced, and the in vivo change (kinetics) of the radioactivity concentration in a non-equilibrium state is measured by PET imaging. Although the half-life of radioactive ¹⁵ O is about 2 minutes, the next labeled compound C ¹⁵ O ₂ is administered continuously for a short time with a short time difference without waiting for the disappearance of the previously administered ¹⁵ O ₂ due to decay. . Thereafter, the radioactivity concentrations of the two labeled compounds decay simultaneously. Thereby, PET imaging of two drugs can be performed continuously once, and the examination time is shortened. However, with this method, the radioactivity required for the inspection must be supplied within a short time limit. However, since the conventional drug supply system was used, the quality of the drug could not be verified within the time limit, and the drug quality test was performed after the fact.

International Publication No. 2006-043674

Chmielowska et al., J Cereb Blood Flow Metab 19: 570-582 (1999)

  An object of the present invention is to provide a labeled compound supply system suitable for an O-15 labeled gas-PET rapid inspection method.

The labeled compound supply system according to the present invention is for sequentially synthesizing at least labeled gas ¹⁵ O ₂ and C ¹⁵ O ₂ using a target box containing a target of accelerated particles of a cyclotron and O-15 generated in the target box. A gas delivery line for delivering the labeled gas, a vacuum pump connected to the gas delivery line in the vicinity of the target box, and a gas delivery line for introducing nitrogen gas into the gas delivery line. A nitrogen gas introducing device to be connected and a sequencer are provided. The gas delivery line is arranged from the target box, through the synthesizer, to the suction pump for collecting the labeled gas delivered in the gas delivery line, and flows between the synthesizer and the suction pump toward the subject. A branch with the road is provided. The sequencer is electrically coupled to the target box, the synthesizer, the gas delivery line, the vacuum pump and the nitrogen gas introduction device, and the replacement of the target in the target box and the cleaning of the gas delivery line and the filling of the new gas and the synthesizer The labeling gas is automatically synthesized. Preferably, a quality confirmation device for confirming the quality of the labeled gas synthesized by the synthesizer is further provided on the downstream side of the branch portion of the gas delivery line so that the labeled gas can be administered after the quality confirmation.

  Preferably, the vacuum pump and the nitrogen gas introducing device have a performance capable of completing the replacement of the target in the target box and the cleaning of the gas delivery line within 2 minutes. Preferably, the synthesizing apparatus, the quality confirmation apparatus, and the gas delivery line are provided with performance capable of completing the supply and quality confirmation of the synthesized labeled compound within 3 minutes. The sequencer also replaces the target in the target box with a vacuum pump, nitrogen gas introduction device and gas delivery line, cleans the gas delivery line and fills with new gas, and supplies the labeled compound synthesized by the synthesizer. Preparation can be completed within 10 minutes.

  In the labeled compound supply system described above, (1) a vacuum pump is connected to the gas delivery line in the vicinity of the target box, and (2) nitrogen gas is introduced into the gas delivery line. Further, (3) a quality confirmation device is arranged on the gas delivery line on the downstream side of the concentration stabilization device and immediately after that. All of these configurations may be combined as described above, but either alone or in combination, the sequencer is ready to supply the labeled compound before the radioactivity in the body disappears (eg, within 10 minutes). Allow completion.

  Adapted to the O-15 labeled gas-PET rapid test method, the administration interval in continuous administration of labeled gas can be shortened, and the quality of the labeled gas can be verified before being given to the subject.

Schematic diagram of a rapid test compatible labeled compound supply system Diagram showing inspection procedure by O-15 labeled compound-PET rapid inspection method Sequence control flowchart

  Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings.

In the O-15 labeled gas-PET rapid test method, which sequentially administers _two labeled compounds ¹⁵ O ₂ and C ¹⁵ O ₂ , each labeled compound is given for a short time, and then the decay of the radiation concentration is caused by a PET device. Measured in Here, the second labeled compound is administered before the first labeled compound is sufficiently attenuated, after which the simultaneous decay of the two labeled compounds is measured. In WO 2006-036774, in the continuous administration of two drugs ( ¹⁵ O ₂ and H ₂ ¹⁵ O, where H ₂ ¹⁵ O is a liquid), 3 minutes have elapsed since the administration of the first drug. In addition, a second drug is administered. This is a generalization of the simple subtraction method proposed by Chmielowska et al. (J Cereb Blood Flow Metab 19: 570-582, 1999) when O-15 labeled water is continuously administered at intervals of 6 minutes. , Enabling shorter administration times and administration of different radiopharmaceuticals. When administered two labeled gas ¹⁵ O ₂ and C ¹⁵ O ₂ independently at rapid test, ¹⁵ O ₂ and C ¹⁵ O such as quality of oxygen consumption and cerebral blood flow images obtained in the best by calculation The optimal measurement time at the time of ₂ administrations is about 3 minutes and 1.5 minutes, respectively. However, the present inventors have determined the time from the end of administration of the first drug to the administration of the second drug (first Note that the PET test can be performed without waiting for the disappearance of radioactivity due to attenuation for the measurement time of the first drug, and after the lapse of 3 minutes, which is the optimal imaging collection time, from the end of the administration of the first drug A labeling compound supply system has been developed that allows the supply of two drugs and allows quality pre-testing prior to that. At present, the time from the end of the administration of the first drug to the administration of the second drug is about 5 minutes. Needless to say, this administration interval improves the performance of devices incorporated in the labeled compound supply system. To make it even shorter. In general, the O-15 labeled gas-PET rapid inspection method can be performed by administering the next labeled gas before disappearance due to attenuation of radioactivity in the body by the administered labeled gas. As described in the above-mentioned report by Chmielowska et al., The time required for the disappearance of ¹⁵ O-labeled gas from the body due to attenuation of radioactivity is typically 10 minutes. In a conventional test in which continuous administration is not performed, a drug is administered after 10 minutes have elapsed from the end of administration.

FIG. 1 shows a schematic configuration of one embodiment of a rapid test-compatible ¹⁵ O-labeled compound supply system capable of pre-qualification of drugs. In this ¹⁵ O-labeled compound supply system, labeled compounds C ¹⁵ O _, ¹⁵ O ₂ and C ¹⁵ O ₂ can be administered sequentially. A facility for performing a PET examination usually includes a cyclotron chamber 10 containing a cyclotron, a hot lab chamber 40, and a PET chamber 50 containing a PET device (positron emission tomography device). Note that the ¹⁵ O-labeled compound supply system of the present invention can also be used in a facility that does not have a hot lab room.

In the cyclotron chamber 10, accelerated O-15 ( ¹⁵ O) is generated by irradiating the target in the target box 12 with accelerated particles generated by a cyclotron (not shown), and ¹⁵ O gas is continuously generated from the target box 12. It is supplied to the synthesizer 14 at a constant flow rate. In the combining device 14, three types of O-15 labeled gas (O-15 labeled carbon monoxide ^{(C 15 O), O-} 15 labeled oxygen ⁽¹⁵ O ₂₎ and O-15 labeled carbon dioxide (C ¹⁵ O ₂₎ ) Can be synthesized in separate synthesis systems 14a, 14b and 14c. Since a method for synthesizing three kinds of labeling compounds and a system therefor are known, a detailed description of the synthesis of the labeling compounds is omitted. The gas delivery line 18 is a pipe arranged from the target box 12 to the suction pump 24 through the synthesis device 14 and the concentration stabilization device 52 in the PET chamber. Various valves and the like are provided in the line between the gas delivery line 18 and various devices connected thereto, and the opening and closing thereof can be electrically controlled. However, the description thereof is omitted for simplification.

  The vacuum pump 16 is a vacuum pump attached to the target box 12, and is connected to the gas delivery line 18 between the target box 12 and the synthesizer 14, and the exhausted gas is stored in the storage tank 20. When the replacement of the target is necessary, the target box 12 is set to a negative pressure by using the exhaust by the vacuum pump 16 and a new target is introduced, so that the target in the target box 12 can be quickly replaced.

  Similarly, a nitrogen gas introducing device 22 for cleaning the gas delivery line is connected to the gas delivery line 18 between the target box 12 and the synthesis device 14. The nitrogen gas introducing device 22 fills the synthesizing device 14 and the gas delivery line 18 with nitrogen gas, and after the introduction is stopped, the gas is pumped downstream by the suction pump 24, thereby cleaning the gas delivery line, that is, removing the remaining labeled gas. It can be done quickly. In general, an inert gas typified by nitrogen gas may be introduced for cleaning. The nitrogen gas introduction device 22 is an example of an inert gas introduction device.

  In the PET chamber 50, the labeling gas is supplied to the concentration stabilizing device 52. The concentration stabilizing device 52 is a buffer device that operates so as to keep the radioactive concentration constant by increasing the flow rate of mixed non-activated gas when the radioactive concentration decreases. The concentration stabilizing device 52 supplies the labeled gas with the stabilized radioactivity concentration per time to the inhalation mask 54 worn by the subject (subject). Thus, when the labeled gas is supplied to the subject, collection of PET imaging data is started. With a PET device (not shown), a time series curve is obtained for each radioactivity distribution in the brain by reconstructing the obtained projection data (called sinogram) of the radioactivity distribution in the brain every time. . The concentration stabilizing device 52 is not required if the irradiation dose of the cyclotron is constant. In this case, a trident channel is used instead of the concentration stabilizing device, and the flow from the trident channel to the suction mask 54 is used. A valve that allows gas to flow through the path may be provided. By operating the valve, the gas can flow toward the suction mask 54.

  A quality confirmation device 56 for confirming the quality of the labeled gas is connected to the gas delivery line 18 immediately after the downstream side of the concentration stabilization device 52. The quality confirmation device 56 is a device that measures the radiochemical purity of the labeled compound, and specifically measures using a gas chromatograph. The quality confirmation device 56 enables the pharmaceutical person in charge to confirm the test result by automatic operation. The pharmaceutical person in charge can confirm the quality of the labeled compound based on the result. The gas transported through the gas delivery line 18 is collected by the suction pump 24 installed in the cyclotron chamber and stored in the storage tank 20. The gas from the suction mask 54 is collected by the suction pump 26 installed in the cyclotron chamber and stored in the storage tank 28.

Conventionally, a quality confirmation apparatus has been installed in a hot lab room so that pharmaceutical personnel in the hot lab room can directly manage the quality confirmation apparatus for quality verification. In this case, due to the interruption of the ¹⁵ O gas supply caused by the switching of the flow path for confirming the quality of the ¹⁵ O labeled gas, concentration stabilization and delay in inhalation start were unavoidable, and it was not possible to respond to rapid inspection. In this system, since the quality confirmation device 56 is installed after the concentration stabilizing device 52, there is no temporary blockage of the ¹⁵ O labeled gas to the concentration stabilizing device 52 due to the switching of the flow channel.

  The PET room 50 is provided with a sequencer (sequence device) 58 that performs sequence control in the labeled compound supply system, and a pharmaceutical person in charge operates the sequencer 58 in the PET room 50. The sequencer 58 is a programmable logic controller, for example. The sequencer 58 is electrically coupled to the nitrogen gas introduction device 22, the vacuum pump 24, the synthesis device 14, the suction pumps 24 and 26, the concentration stabilization device 52, the suction mask 54, the quality confirmation device 56, various valves, a PET device, and the like. The operation timing is controlled. Therefore, for example, the synthesis device 14 has an external input / output terminal for synchronizing with the collection of the PET imaging device. Detailed descriptions of various electrical couplings for sequence control are omitted.

  In the case where the pre-verification is not performed, the quality confirmation device 56 is not necessarily provided. Even in such a case, by using this labeled compound supply system, the administration interval of the labeled compound can be shortened, and the measurement time can be brought close to, for example, the above-mentioned optimum time of 3 minutes and 1.5 minutes.

FIG. 2 schematically shows an example of an inspection procedure capable of completing the inspection within 20 minutes in the O-15 labeled gas-PET rapid inspection method. During the examination, the head of the subject (not shown) is fixed on the bed within the field of view of the PET apparatus. Blood collection from the artery is started before the first drug administration and is continued during the test. This gives a total radioactivity concentration curve in blood. In the example of FIG. 2, three types of labeled compounds are administered to the subject in the order of C ¹⁵ O, ¹⁵ O ₂ and C ¹⁵ O ₂ . The drug administration times of C ¹⁵ O, ¹⁵ O ₂ and C ¹⁵ O ₂ are set to 30 seconds, 1 minute and 1 minute, respectively. This drug administration time is the time required to transfer the radioactivity necessary for the examination into the brain, and is set empirically. The radioactivity concentrations of C ¹⁵ O, ¹⁵ O ₂ and C ¹⁵ O _{2 at} the set drug administration time are about 2200 MBq / min, 45000 MBq / min, and 4000 MBq / min, respectively, in the case of two-dimensional PET imaging. However, in the case of the three-dimensional PET imaging method, it is reduced by about one digit. First, the labeled compound C ¹⁵ O is measured, but unlike the steady-state method, the decay of the radioactivity concentration is measured after short-time administration. Next, continuous administration of labeled compounds ¹⁵ O ₂ and C ¹⁵ O ₂ is performed, but after one labeled compound is administered first, the other label is not waited for sufficient attenuation of the previously administered labeled compound. The compounds are subsequently administered with a short time lag, with which ¹⁵ O ₂ and C ¹⁵ O ₂ PET imaging data collection is continuously performed without interruption. The time difference between two consecutively administered labeling compounds is typically 5 minutes, but as much as possible as long as the quality of the functional image based on the administration of the first drug is longer than the optimal acquisition time. Short is desired. Therefore, after the completion of administration of the ¹⁵ O _2, is immediately synthesized starting the C ¹⁵ O _2, when its quality is confirmed, the synthesized C ¹⁵ O ₂ is administered. In this example, the time difference between administrations is 5 minutes. Note that the order of administration of the three types of labeled compounds C ¹⁵ O, ¹⁵ O ₂ and C ¹⁵ O ₂ is not limited to this, and for example, ¹⁵ O ₂ may be continuously administered after C ¹⁵ O _2. The explanation is omitted.

In the example described above, in the continuous administration of labeled compounds ¹⁵ O ₂ and C ¹⁵ O ₂ , the administration of C ¹⁵ O ₂ must be started 5 minutes after the end of ¹⁵ O ₂ administration, so that the synthesized C ¹⁵ pre-test of the quality of O _2, it is necessary to end prior to the administration of the C ¹⁵ O ₂ from the completion of the administration of the ¹⁵ O _2. In order to quickly start the synthesis and quality confirmation of the labeled compound, the supply system shown in FIG. 1 has the following features. First, (1) the quality confirmation device 56 is arranged immediately after the downstream side of the concentration stabilization device 52 to maintain a continuous ¹⁵ O labeled gas supply. As described above, even if the quality confirmation device 56 is installed immediately after the downstream side of the concentration stabilization device 52, the fastest synthesis device or quality confirmation device is used from the start of synthesis of the labeled gas to be administered next to the quality confirmation. It took about 3 minutes. In other words, the synthesizer 14, the gas delivery line 18 and the quality confirmation device 56 used here have the performance that can be completed within 3 minutes from the start of synthesis of the labeled gas to be administered to the quality confirmation. For this reason, it is necessary to complete the quick replacement of the remaining gas and the preparation for synthesis in the gas delivery line 18 within two minutes. Here, in order to synthesize C ¹⁵ O _2, the target in the target box 12 must also be exchanged. Therefore, (2) the vacuum pump 16 is connected to the gas delivery line 18 near the target box 12, and (3) the nitrogen gas introducing device 22 is connected to the gas delivery line 18. Further, (4) a suction pump 24 that sucks the gas delivery line 18 is used to remove nitrogen in the gas delivery line 18. Thus, the ¹⁵ O ₂ target is evacuated from the target box 12 by the vacuum pump 16, and at the same time, the labeling gas remaining in the gas delivery line 18 is quickly removed. 22, the C ¹⁵ O ₂ target is introduced into the target box 12 and the gas delivery line 18. (The C ¹⁵ O ₂ target is a gas composed mostly of nitrogen.) Here, by selecting an optimal vacuum pump 16 and nitrogen gas introducing device 22 that are currently available, the residual gas in the gas distribution line 18 Rapid exchange and synthesis preparations can be completed quickly within 2 minutes. In addition, although the length of the gas delivery line 18 is 60 m in the example of FIG. 1, this is a standard length. In other words, the vacuum pump 16, the nitrogen gas introducing device 22 and the gas delivery line 18 used here are capable of completing the replacement of the target in the target box 12 and the cleaning of the gas delivery line 12 within 2 minutes. Is provided. Thereafter, irradiation of the exchanged target and synthesis of a new labeled gas by the synthesizer 14 are started, and the synthesized labeled gas is transported to the quality confirmation device 56 through the gas delivery line 18 and tested after the quality confirmation. It is administered to a person. Thus it was reduced ¹⁵ O-labeled gas quality verification time ⁽¹⁵ hours from O synthetic preparation of labeled gas to quality check) in 5 minutes. This pre-testing of the labeled compound is possible only for the above-described labeled compound supply system.

  In the rapid test method described in International Publication No. 2006-043674), CO administration is unnecessary, but in the above example, CO administration is performed. By taking a CO image and comparing similar images (blood volume) calculated from a protocol that does not require CO, an image containing a large amount of arterial components even with the same blood volume and an entire blood volume image are obtained. Compare them.

In a comparative example in which two target boxes are exchanged, a ¹⁵ O ₂ target for synthesizing CO and O ₂ and a C ¹⁵ O ₂ target for synthesizing CO ₂ are used. In the labeled compound supply system of FIG. 1, since the vacuum pump 16 is attached to one target box 12, the target can be replaced in a shorter time (within 2 minutes) than the comparative example in which the target box is replaced. . In the case of a cyclotron in which two target boxes can be installed in parallel, it is not necessary to exhaust the target box rapidly.

The inspection procedure of FIG. 2 will be further described. In the case of the inspection of the first administered drug C ¹⁵ O, the cyclotron is operated to generate ¹⁵ O in the target box, and the synthesis apparatus 14 synthesizes C ¹⁵ O to the PET chamber Send to. C ¹⁵ O is tested for quality by the quality confirmation device 56, then sent from the concentration stabilization device 52 to the inhalation mask 54, and administered to the subject for a short time (30 seconds). Thereafter, PET imaging data of the head is collected by the PET device. Data collection time is 6 minutes.

Next, ¹⁵ O ₂ and C ¹⁵ O ₂ are administered sequentially. When the administration of the above-described drug C ¹⁵ O is completed, first, nitrogen gas is introduced into the synthesizer 14 and the gas delivery line 18 by the nitrogen gas introduction device 22 to clean the gas delivery line 18. (In this case, the target is not replaced.) Next, the cyclotron is operated to generate ¹⁵ O in the target box, ¹⁵ O ₂ is synthesized in the synthesizer 14 and sent to the PET chamber. ¹⁵ O ₂ is sent to the inhalation mask 54 after quality is verified by the quality confirmation device 56, and is administered to the subject for a short time (1 minute). Thereafter, PET imaging data is collected for 5 minutes. Here, after “5 minutes”, the radioactivity concentration of the administered drug is not yet sufficiently attenuated, but in this rapid test method, the next drug is administered in that state. For this reason, as soon as the above-mentioned administration of ¹⁵ O ₂ for 1 minute is completed, the rapid replacement of the remaining gas and the preparation for synthesis of C ¹⁵ O ₂ are started. First, the target box 12 is evacuated by the vacuum pump 16 and replaced with a C ¹⁵ O ₂ target. At the same time, the nitrogen gas is introduced into the synthesizer 14 and the gas delivery line 18 by the nitrogen gas introduction device 22 and the remaining gas is left. Remove the labeled compound. Further, the introduction of nitrogen is stopped, and the suction pump 24 sucks the gas delivery line 18 from the synthesizer 14 to the suction pump 24 to 73 kPa, and removes nitrogen in the gas delivery line 18. The time required from exhausting the target box 12 to removing nitrogen in the line 18 is within one minute. Then, irradiation to the replaced target is started, and the gas delivery line 18 is filled with nitrogen, and the synthesis preparation is completed within 2 minutes. Synthesis of C ¹⁵ O ₂ is started in the synthesizer 14 and supplied to the PET chamber. The synthesized C ¹⁵ O ₂ is tested for quality by the quality confirmation device 56 within 5 minutes from the start of synthesis, and then administration (1 minute) of C ¹⁵ O ₂ to the subject is started. Here, PET imaging is continued continuously, and imaging data is collected for another 3 minutes. ^The PET imaging by the PET apparatus is completed after data collection for a total of 9 minutes for ¹⁵ O ₂ and C ¹⁵ O ₂ . These series of operations are controlled by automatic sequence control by the sequencer 58. The entire PET examination can be completed in 20 minutes. In this example, the labeled gas C ¹⁵ O ₂ can be administered after the pre-verification. That is, after the subject's ¹⁵ O ₂ inhalation is completed, the inhalation can be started after confirming the quality of C ¹⁵ O ₂ 5 minutes after the start of C ¹⁵ O ₂ synthesis. In this way, the present labeled compound supply system has enabled the pre-verification of the quality of the labeled gas in the rapid inspection method.

As described above, the two drugs ( ¹⁵ O ₂ and C ¹⁵ O ₂ ) are administered sequentially after the collection of C ¹⁵ O PET imaging data is complete. For this continuous administration, an automatic control sequence by the sequencer 48 is executed.

FIG. 3 shows a flow of a continuous administration control program executed sequentially by the sequencer 48. After administration of C ¹⁵ O for a predetermined time (for example, 30 seconds), the nitrogen gas introduction device 22 is set at an appropriate time in consideration of the PET imaging data collection time of C ¹⁵ O and the time required for the pre-verification. Nitrogen gas is introduced into the synthesizer 14 and the gas delivery line 18 (S10), and the gas delivery line 18 is cleaned. That is, the remaining labeled compound is removed and filled with nitrogen gas. Next, the nitrogen gas introduction device 22 is stopped from introducing nitrogen (S12), the synthesis device 14 is started to synthesize ¹⁵ O ₂ (S14), and the quality confirmation device 56 checks the quality of the synthesized ¹⁵ O _2. Is started (S16). The synthesized ¹⁵ O ₂ is sent to the PET chamber 50 through the gas delivery line 18 using nitrogen gas as a carrier gas, and the verification by the quality confirmation device 56 is started. When a predetermined C ¹⁵ O PET imaging data collection time (for example, 6 minutes) elapses and quality confirmation of the synthesized ¹⁵ O ₂ is completed within the predetermined time (5 minutes) (S18), the marker gas supply device The (concentration stabilizing device 52) starts supplying ¹⁵ O ₂ to the suction mask 54, and at the same time, the PET device (not shown) starts collecting PET imaging data (S20). The supply of ¹⁵ O ₂ is terminated in a predetermined time (for example, 1 minute) (S22).

When the administration of the medicine ( ¹⁵ O ₂ ) is completed, the target box 12 is evacuated by the vacuum pump 16 and replaced with the C ¹⁵ O ₂ target by the nitrogen gas introducing device 22 to start irradiation with accelerated particles (S24). Thus, the replacement is completed within one minute, for example. At the same time, nitrogen gas is introduced into the synthesis device 14 and the gas delivery line 18 by the nitrogen gas introduction device 22 (S26), and the gas delivery line 18 is cleaned. In this way, by the sequence control, one of the labeled gases ¹⁵ O ₂ and C ¹⁵ O ₂ is administered to the subject for a predetermined time, and the one of the labeled gases ¹⁵ O ₂ and C ¹⁵ O ₂ is performed. Immediately after completing the synthesis and administration of the labeled gas, the vacuum pump evacuates the target box of the cyclotron and replaces the target in the target box. Nitrogen gas is introduced into the synthesizer.

Next, the introduction of nitrogen by the nitrogen gas introduction device 22 is stopped, and the suction pump 24 sucks the gas delivery line 18 from the synthesizer 14 to the suction pump 24 (S28), thereby removing nitrogen in the gas delivery line. The time required from exhausting the target box 12 to removing nitrogen in the line is within one minute (for example, 50 seconds). Next, the synthesis device 14 starts synthesis of C ¹⁵ O ₂ (S30). The synthesized C ¹⁵ O ₂ is sent to the PET chamber 50 through the gas delivery line 18 using nitrogen gas as a carrier gas, and causes the quality confirmation device 56 to start the C ¹⁵ O ₂ quality test (S32). Pre-verification by the quality confirmation device 56 is performed. For example, when the quality confirmation of the C ¹⁵ O ₂ by the quality confirmation device 56 is completed within 5 minutes from the start of the synthesis, the concentration stabilizing device 52, which is a labeled gas supply device, starts supplying C ¹⁵ O ₂ to the suction mask 54. (S34). When a predetermined supply time (for example, 1 minute) elapses, the synthesis and supply of C ¹⁵ O ₂ are stopped (S36). In this way, the sequence control further stops the nitrogen gas introduction device from introducing nitrogen, causes the suction pump to suck the gas delivery line from the synthesizer to the suction pump, and then causes the synthesizer to supply the labeled gas ¹⁵ O ₂ and The synthesis of the other labeled gas of C ¹⁵ O ₂ is started. Next, let the quality confirmation device confirm the quality of the other labeled gas synthesized, and when the quality of the other labeled gas is confirmed within 5 minutes after the administration of the one labeled gas is completed, The other labeled gas thus synthesized is administered to the subject for a predetermined time.

  Thereafter, when a predetermined time (3 minutes) elapses, collection of PET imaging data is terminated (S38). In this way, by sequence control, after completing the synthesis and administration of the labeled gas, or after completion of the test, the external PET imaging data collection system starts data collection, and data collection is performed after a predetermined time has passed. Stop. Further, after the synthesis and administration of the labeled gas is completed, irradiation of the accelerated particles to the target is started, and at the same time, the target box 12 is sucked, and at the same time, the gas delivery line 18 is put into the nitrogen gas introducing device 22 at a positive pressure. Extrude residual radioactivity at.

  In the case where the order of administration of the two drugs is reversed, a prior quality test can be performed in the same manner.

As described above, in the labeled compound supply system described above, the quality test of the next administered O-15 labeled gas is performed before the radioactivity in the body due to the administered O-15 labeled gas disappears due to attenuation. Multiple O-15 labeled gases can be administered sequentially after pre-testing. Specifically, O-15 labeled gas (O-15 labeled carbon monoxide (C ¹⁵ O), O-15 labeled oxygen ( ¹⁵ O ₂ ) and O-15 labeled carbon dioxide (C ¹⁵ O ₂ )), Each could be administered to the subject after quality confirmation.

  In the labeling compound supply system described above, (1) the vacuum pump 16 is connected to the gas delivery line 18 in the vicinity of the target box 12, and (2) nitrogen gas is introduced into the gas delivery line. The gas introduction device 22 is connected. (3) Further, the quality confirmation device 56 is disposed immediately downstream of the concentration stabilization device 52 in the gas delivery line 18. As explained previously, this reduced the dosing interval to 5 minutes.

In a rapid test method, more generally, when a labeled compound is continuously administered to a subject, after the administration of one labeled gas is completed, the radioactivity in the body by the administered labeled gas is attenuated. The next labeled gas may be administered before disappearing. Therefore, the dosing interval (completion of the preparation for supplying the labeled compound) is within 10 minutes, preferably within 9 minutes, more preferably within 7 minutes, and even more preferably within 5 minutes. Therefore, not all of the above-described three configurations are necessarily provided, and one or two configurations may be combined so that the time condition is satisfied according to the specification of the labeled compound supply system. . For example, only one of the vacuum pump 16 and the nitrogen gas introducing device 22 is arranged, or the quality confirmation device 56 is installed immediately downstream of the concentration stabilizing device 52 so that the dosing interval is within 10 minutes. The sequence control may be performed. (In the above example, the synthesis of ¹⁵ O ₂ is performed without evacuation by a vacuum pump.)

  In the above sequence control example, since the administration is performed at intervals of 5 minutes or less, the rapid replacement of the remaining gas in the gas delivery line 18 and the preparation for synthesis are completed within 2 minutes, and the synthesis and quality check are performed within 3 minutes. Was finished. However, more generally, as long as radioactivity in the body disappears due to attenuation as described above (for example, within 10 minutes), it is only necessary to check the quality. It may be processed in a short time.

  In the labeled compound supply system shown in FIG. 1, for example, when the vacuum pump 16, the nitrogen gas introduction device 22 or the quality confirmation device 56 is not included or used, the control of the device is performed in the sequence control of FIG. It can be omitted.

The labeled compound supply system may further include a second synthesizer (not shown) for synthesizing ¹⁵ O ₂ to ¹⁵ O labeled water (H ₂ ¹⁵ O). This synthesizer synthesizes H ₂ ¹⁵ O by reacting with hydrogen when ¹⁵ O ₂ sent to the subject is branched and supplied in the PET room. ¹⁵ O labeled water can be administered instead of C ¹⁵ O ₂ gas.

  12 target box, 14 synthesis device, 16 vacuum pump, 18 gas delivery line, 22 nitrogen gas supply device, 52 concentration stabilization device, 54 suction mask, 56 quality confirmation device, 58 sequencer.

Claims (4)

A target box containing cyclotron accelerated particle targets;
A synthesis device for sequentially synthesizing at least the labeled gases ¹⁵ O ₂ and C ¹⁵ O ₂ using O-15 generated in the target box;
A gas delivery line for delivering the labeled gas, wherein the synthesis is arranged from the target box to the suction pump for collecting the labeled gas delivered in the gas delivery line through the synthesis device, A gas delivery line provided with a branch between the apparatus and the suction pump and a flow path toward the subject ;
A vacuum pump connected to the gas delivery line in the vicinity of the target box;
A nitrogen gas introduction device for introducing nitrogen gas into the gas delivery line, the nitrogen gas introduction device connected to the gas delivery line;
A concentration stabilizing device for stabilizing and supplying the concentration of the labeled gas synthesized in the synthesizing device, the concentration stabilizing device provided at a branch portion of the gas transfer line;
A quality confirmation device for confirming the quality of the labeled gas synthesized by the synthesis device before being supplied into the body of a subject, and is connected downstream of the concentration stabilization device of the gas delivery line. A quality confirmation device,
Filling the cleaning and novel gas exchange and the gas delivery line of the target in the previous SL target box, and a sequencer for automatically performing the quality check by synthesis and the quality confirmation apparatus of labeled gas by the synthesizer ,
The sequencer supplies the other labeled gas into the subject's body before the radioactivity in the subject's body due to one of the labeled gases ¹⁵ O ₂ and C ¹⁵ O ₂ disappears due to attenuation. Thus, the labeled compound supply system that performs sequence control on the target box, the synthesis device, the gas delivery line, the vacuum pump, the nitrogen gas introduction device, and the quality confirmation device . The synthesis apparatus further comprising: a synthesis system for synthesizing the C ¹⁵ O, labeled compound supply system described in claim 1. The labeled compound supply system according to claim 1 or 2 , wherein the synthesizer further includes a _second synthesizer for synthesizing ¹⁵ O ₂ to ¹⁵ O labeled water (H ₂ ¹⁵ O). The labeled compound supply system according to any one of claims 1 to 3 , wherein the synthesizer further includes an external input / output terminal for synchronizing with the collection of the PET imaging device.

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