JPH0469088B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention is applicable to medical diagnosis using, for example, radioisotope (RI), that is, radioactive carbon isotope ¹¹ C, synthesized using a small cyclotron.
This is related to equipment that synthesizes ¹¹ C into hydrogen cyanide, and is used for new diagnostics such as quantifiers for various organs including the brain, dynamic diagnosis, early detection of stroke, myocardial infarction, and malignant tumors, and investigation of causes of mental illness. It is something to do. [Prior Art] Cyclotron nuclear medicine is a method of medical diagnosis using short-lived positron-emitting species such as ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F as physiological tracers. In the target system of the cyclotron, these species are produced in simple chemical forms such as inorganic gases, so they are used for diagnosis either as they are or after being converted into more complex chemical forms. Among ¹¹ C, ¹³ N, ¹⁵ O, and ¹⁸ F, ¹¹ C is an isotope of the element that forms the skeleton of organic compounds, so
It has the widest applicability and is capable of labeling many important biological substances. The synthesis of ¹¹ C-standard compounds is partly carried out using ¹¹ CO ₂ or ¹¹ CO produced in the target system as a raw material, but most of the synthesis is carried out via C ₁ compounds as synthetic intermediates. The most widely used _C1 compound is ^11C -hydrogen cyanide ( ^H11CN ).
It is possible to obtain labeled substances of many important biological substances such as sugars, amino acids, and amines from H ¹¹ CN. However, radionuclides such as Kawaru ¹¹ C have a half-life of 20
Since it has a short lifespan of about 1 minute, the labeled synthesis must be carried out quickly, and a large amount of radioactivity must be handled at the starting stage, so there is a risk of exposure to radiation for the workers, and the synthesis is carried out by skilled synthesis techniques. It was impossible for routine nuclear medicine diagnosis. [Object of the present invention] The purpose of the present invention is to automate the synthesis of ¹¹ C radionuclides, and to produce H ¹¹ CN, which is an intermediate material for synthesizing various labeled compounds, online. be. [Configuration of Embodiment] An embodiment of the present invention will be described in detail below with reference to the drawings. As shown in the first diagram, a cylinder 1 filled with _N2 gas, which is a raw material for hydrogen cyanide containing the carbon isotope ^11C , is communicated with a target box 3 of a small cyclotron 2, and this target box 3 is connected via a pump 4 to ^11CO2 gas. It communicates with the main pipe 5 of an apparatus for synthesizing H ¹¹ CN using H 11 _CN as a raw material. This ¹¹ C-hydrogen cyanide (H ¹¹ CN) production equipment is
It is divided into part 6, which reduces ¹¹ CO ₂ to ¹¹ CH ₄ using H ₂ and a Ni catalyst, and part 7, which synthesizes H ¹¹ CN with ¹¹ CH ₄ and NH ₃ . As shown in the first diagram, in the part 6 where ¹¹ CH ₄ is reduced, the H ₂ gas cylinder 10 is connected to the valve V ₁ ,
A main pipe furnace 5 is communicated through a thermal mass flow controller 11, and a column 13 containing a reduction catalyst and a soda lime column 14 in an electric furnace 12 are connected in series to the main pipe 5. As shown in the second diagram, an ammonia gas cylinder 15 is connected to a valve V ₃ on the downstream side of the valve V ₂ in the main pipe 5.
It is connected via a mass flow controller 16, and its main line 5 is connected to a container 19 for storing liquefied NH ₃ from a Duer bottle 18 cooled with dry ice 17.
It communicates with the bottom of. A liquid level sensor 21 is deeply inserted into the Teflon joint 20 fitted to the upper part of this container 19, and a signal from this liquid level sensor 21 is used to control the valve.
Control V ₃ . The outlet of this container 19 is a valve V ₄ ,
It communicates with the ammonia gas outlet 22 through the check valve CV ₁ , and also has a pressure control valve V _5.
communicates with the vacuum outlet 23 through this valve.
V ₅ is controlled by a signal from a pressure sensor 24 connected thereto. The outlet of this vessel 19 is then connected to the inlet of a platinum column 26 in an electric furnace 25 via a valve _V6 ,
The outlet of this platinum column 26 is connected to a phosphorus pentoxide column 28 of a purifier 27, a check valve CV ₂ , and a valve
It communicates with the lower part of the container 30 of the dewar bottle 29 via V ₇ , and the outlet of this container 30 communicates with the outlet 31 via the valve V ₈ . Note that this purification device 27
The internal piping shall be treated with acid. The entire H ¹¹ CN manufacturing equipment described above is installed in a radiation-protected hot cell, and can be operated remotely using an external control panel without exposing the human body to radiation. Each step of the above-mentioned valves V ₁ , V ₂ ...V ₈ , mass flow controllers 11, 16, electric furnaces 12, 25
The operations at P ₁ , P ₂ , ...P ₉ are shown in the table below.

【table】

[Operation of the present invention]

The operation of this device will be explained next. First, in step _P1 , open valves V ₄ , V ₂ , V ₆ , and V ₅ , open mass flow controllers 11 and 16,
Evacuate the inside of the piping. Further, electric current is passed through the electric furnaces 12 and 25. Next, in step _P2 , the valve _V3 is opened, the mass flow controller 11 is closed, and the mass flow controller 16 is set to a set value to store the liquefied NH ₃ in the container 19. Next, in step _P3 , the electric furnaces 12 and 25 are controlled to a predetermined temperature. Next, in step _P4 , the cyclotron 2 and pump 4 are started, and in step _P5 , the valve _V1 is opened.
As a result, the nitrogen gas in the cylinder 1 is sent to the target box 3, and a part of it is ¹⁴ N (P, α).
In the ¹¹ C reaction, the carbon isotope becomes ¹¹ C, combines with oxygen, becomes ¹¹ CO ₂ , and is sent into the main pipe 5 by the pump 4. On the other hand, the _H2 gas in the cylinder 10 is controlled by a valve.
V ₁ through thermal mass flow controller 1
1, the Ni gas is sent to the main pipe 5 while its flow rate is controlled, mixed with radiation gas ( ¹¹ CO ₂ ) from the target box 3, and charged into the Ni gas installed in the electric furnace 12.
It is heated to 500 to 600°C in a column 13 containing a catalyst to reduce ¹¹ CO ₂ and synthesize methane gas of ¹¹ CH ₄ . These gases are then sent to the soda lime column 14 where unreacted ¹¹ CO ₂ is absorbed by the soda lime. Next, in step P ₆ , valves V ₂ and V ₆ are opened, and ¹¹ CH ₄
The gas is then sent to section 7 where ¹¹ CN is synthesized.
In the section 7 for synthesizing H ¹¹ CN, the ammonia gas in the cylinder 15 is previously sent into the dewar bottle 18 via the valve V _{3 and} the mass flow controller 16 in step P2, and the NH ₃ is heated to -80°C.
The liquid is cooled to a dry ice temperature of 200 mL, and is liquefied and stored in a container 19 of a Duer bottle 18. The purpose of liquefying NH ₃ is to trap moisture at low temperatures, which would interfere with the reaction. The liquid level of NH ₃ is monitored by a liquid level sensor 21 using infrared rays, and when a predetermined liquid level is reached, the reaction automatically proceeds. ¹¹ ch ₄ for this
Mixing of ¹¹ CH ₄ and NH ₃ is carried out by passing.
The pressure of this mixed gas is controlled to be below a certain maximum pressure Pmax in step _P7 . Next, in step _P8 , valves _V7 and _V8 are turned on,
The above mixed gas is sent into the platinum column 26, heated to around 1000°C by the electric furnace 25, and converted into ¹¹ CH ₄ +
It is converted to H ¹¹ CN by the reaction of NH ₃ →H ¹¹ CN + 3H ₂ . This gas then passes through a P ₂ O ₅ column 28 in a purifier 27 to remove excess NH ₃ . The thus purified H ¹¹ CN is sent to the container 30 of the dewar bottle 29 through the check valve CV ₂ and collected at dry ice temperature or with an aqueous alkaline solution. This check valve CV ₂ prevents backflow of solution 33 in this tube. Finally, in step _P9 , the valves V ₁ , V ₂ , V ₄ , V ₆ ,
V ₇ and V ₈ close, completing the synthesis work. [Effects] As described above, according to the present invention, ¹¹ C hydrogen cyanide can be automatically synthesized and workers can perform the work safely without risk of exposure.
Therefore, the present invention enables online synthesis of H ¹¹ CN, which facilitates the standard synthesis of important biological substances such as sugars and amino acids, and allows routine synthesis using these standard compounds even in general hospitals without specialists. This makes nuclear medicine diagnosis possible and greatly contributes to the spread and development of cyclotron nuclear medicine.

[Brief explanation of drawings]

Figures 1 and 2 show ¹¹ CO ₂ and H ₂ in one embodiment of the present invention.
Part reduced by Ni catalyst and ¹¹ by CH ₄ and NH ₃
Explanatory diagram showing the parts for synthesizing H ¹¹ CN, Part 3
The figure is a block diagram of the control device, and FIG. 4 is its flow diagram. 1...Cylinder, 2...Small cyclotron, 3
...Target Box, 4...Pump, 5...
Main pipeline, 6, 7... Equipment, 10... _H2 gas cylinder, 12... Electric furnace, 13... Ni column, 14
...soda lime column, 15...ammonia gas cylinder, 19...container for liquefying _NH3 ,
V ₅ ... pressure control valve, 25 ... furnace, 26 ...
...Platinum column, 27...Purification device, P ₁ , P ₂ , P ₃
...Step.

Claims (1)

[Claims] 1 A cylinder filled with N ₂ gas, which is a raw material for hydrogen cyanide containing the carbon isotope ¹¹ C, is connected to a target box in a small cyclotron, and this target box synthesizes H ¹¹ CN using ¹¹ CO ₂ as a raw material via a pump. communicates with the main pipe of the device,
A H ₂ gas cylinder is connected to this main pipe, a column containing a reduction catalyst and a soda lime column in an electric furnace are connected in series to this main pipe, and then an ammonia gas cylinder is connected to this main pipe. The outlet of _this container is connected to a pressure control valve and a platinum column in the furnace, and the outlet of this platinum column is connected to a purification device. A means for sending the produced ¹¹ CO ₂ gas together with H ₂ gas to a furnace containing a reduction catalyst, and a means for sending the ¹¹ CH ₄ gas synthesized in this furnace.
means for sending the NH ₃ gas to a platinum column in the furnace;
¹¹ C-Hydrogen cyanide production apparatus comprising means for sending H ¹¹ CN synthesized in this platinum column to a purification apparatus.