CN111393306A - Apparatus for synthesizing radioiodinated compound - Google Patents

Abstract

The present invention relates to a device for synthesizing a radioiodinated compound. The present invention addresses the problem of achieving a good synthesis yield of a radioiodinated compound. The solution is a synthetic apparatus (1) for a radioiodinated compound, which is used for synthesizing a radioiodinated compound of a radioiodinated compound by an iodine exchange reaction from a nonradioactive iodine compound, comprising: the reaction vessel (10) for causing a nonradioactive iodine compound to flow back in a solution state and to contact radioactive iodine to perform an iodine exchange reaction, the heating unit (20) for heating the reaction vessel (10) from below, and the tubular return pipe (30) connected to the reaction vessel (10) for causing a reaction solution for the iodine exchange reaction to flow back, wherein the return pipe (30) is disposed above the position of the heating unit (20), a part (301) of the return pipe (30) is provided in a spiral shape above the reaction vessel (10), and a part (301) of the return pipe (30) is disposed horizontally.

Description

Synthesis device for radioactive iodine-labeled compounds

technical field

The present invention relates to a synthesis device for radioactive iodine-labeled compounds.

Background technique

As a synthesis method of a radioactive iodine-labeled compound, a synthesis method based on an exchange reaction between a non-radioactive compound and radioactive sodium iodide is known. Such synthetic methods have been used for N-isopropyl-4-iodoamphetamine ( ¹²³ I) ( ¹²³ I-IMP) used in cerebral blood flow imaging, 15-( Synthesis of 4-iodophenyl)-3(R,S)-methylpentadecanoic acid ( ¹²³ I) ( ¹²³ I-BMIPP).

Among them, ¹²³ I-IMP can be synthesized by, for example, heating an aqueous solution of non-radioactive N-isopropyl-4-iodoamphetamine in the presence of copper sulfate and formic acid to reflux and contacting with [ ¹²³ I]sodium iodide.

Patent Document 1 describes a method for synthesizing a radioiodine-labeled compound while heating and refluxing in this way.

prior art literature

Patent Literature

Patent Document 1: Japanese Patent Laid-Open No. 55-73640

SUMMARY OF THE INVENTION

Invention to solve problem

However, in the above-mentioned Patent Document 1, there is absolutely no mention of the specific configuration of the synthesis apparatus related to heating and refluxing, and the inventors of the present application have found that, depending on the installation conditions of the reflux tube in the synthesis apparatus of the radioactive iodine-labeled compound, It is difficult to achieve good synthetic yields of radioiodinated compounds.

The present invention has been made in view of the above-mentioned problems, and provides an apparatus for synthesizing a radioiodine-labeled compound having a structure capable of realizing a good synthesis yield of a radioiodinated compound.

solution to the problem

The present invention provides a device for synthesizing radioactive iodine-labeled compounds, which is characterized in that it is used for synthesizing radioactive iodine-labeled compounds from non-radioactive iodine compounds through iodine exchange reaction,

The synthesis device has:

A reaction vessel for carrying out the aforementioned iodine exchange reaction by refluxing the aforementioned non-radioactive iodine compound in a solution state and contacting it with radioactive iodine;

A heating section that heats the aforementioned reaction vessel from below; and

A tubular reflux pipe connected to the aforementioned reaction vessel for refluxing the reaction solution of the aforementioned iodine exchange reaction,

The return pipe is arranged above the position of the heating part,

A part of the above-mentioned return pipe is arranged in a vortex above the above-mentioned reaction vessel,

The said part of the said return pipe is arrange|positioned horizontally.

effect of invention

According to the present invention, by swirling a part of the reflux tube above the reaction vessel, it is possible to achieve a good synthesis yield of the radioiodine-labeled compound.

Description of drawings

1 is a schematic diagram of an apparatus for synthesizing a radioactive iodine-labeled compound according to an embodiment.

2( a ) is a schematic plan view showing Modification 1 of a part of the return pipe, and FIG. 2( b ) is a schematic plan view showing Modification 2 of a part of the return pipe, (c) of FIG. 2 is a schematic plan view showing Modification 3 of a part of the return pipe.

[ Fig. 3] Fig. 3 is a schematic diagram of an apparatus for synthesizing a radioactive iodine-labeled compound according to a comparative example.

[ Fig. 4] Fig. 4 is a schematic diagram showing a part of the return pipe of the apparatus for synthesizing a radioactive iodine-labeled compound according to the embodiment and its periphery (a view of the top plate of the clean bench looking up).

[ Fig. 5] Fig. 5 is a schematic diagram of an apparatus for synthesizing a radioactive iodine-labeled compound according to an embodiment.

Description of reference numerals

1 synthesis device

10 Reaction Vessels

20 Heating section

30 Return line

30a one end

The other end of 30b

50 valve

60 Shade

90 Synthesizers

101 Main body

102 Connector

103 Input port

201 Thermal medium container

202 heater

301 part

301a one end

301b at the other end

302 The first middle part (middle part)

303 Second Intermediate Part

401 Trap

402 Activated carbon trap

403 tubes

901 Return Line

902 Trap

W top plate

Detailed ways

Hereinafter, embodiments of the present invention will be described with reference to the drawings. In addition, in all drawings, the same code|symbol is attached|subjected to the same component, and description is abbreviate|omitted suitably.

FIG. 1 is a diagram showing an apparatus 1 for synthesizing a radioactive iodine-labeled compound according to an embodiment. The synthesis apparatus 1 is a synthesis apparatus for a radioactive iodine-labeled compound for synthesizing a radioactive iodine-labeled compound from a non-radioactive iodine compound through an iodine exchange reaction, and as shown in FIG. The reaction vessel 10 for performing the iodine exchange reaction by refluxing and contacting with radioactive iodine, the heating section 20 for heating the reaction vessel 10 from below, and the tubular reflux tube 30 connected to the reaction vessel 10 for refluxing the reaction solution of the iodine exchange reaction . The return pipe 30 is arranged above the position of the heating unit 20 . A part 301 of the reflux pipe 30 is provided above the reaction vessel 10 in a spiral shape or a meander shape (see Fig. 2(b) and Fig. 2(c) ).

In this specification, "up" means the direction opposite to the direction of gravity, and "down" means the same direction as the direction of gravity.

According to the present embodiment, by providing a part 301 of the reflux tube 30 in a spiral shape or a meander shape above the reaction vessel 10 , it is possible to achieve a good synthesis yield of the radioiodine-labeled compound.

More specifically, in the case of the present embodiment, a part 301 of the recirculation pipe 30 is provided in a spiral shape above the reaction container 10 , and a part 301 of the recirculation pipe 30 is arranged horizontally.

Here, the "horizontal" arrangement means that the spiral portion (a portion 301 ) of the return pipe 30 may not be spirally advanced in the vertical direction like a spiral staircase, but may be arranged substantially horizontally. In other words, not only the case where the part 301 is clearly arranged horizontally, but also the case where it is arranged substantially horizontally is included. It should be noted that a part 301 may be slightly inclined. When the diameters (winding diameters) of the respective winding portions in the part 301 are equal to each other, it is preferable that the respective winding portions are in contact with each other. In addition, each winding part is a part formed by winding the return pipe 30 once, and the winding parts are mutually connected.

Synthesis device 1 can be used for N-isopropyl-4-iodoamphetamine ( ¹²³ I) ( ¹²³ I-IMP), 15-(4-iodophenyl)-3(R, used in myocardial fatty acid metabolism imaging, Synthesis of radioiodinated compounds such as S)-methylpentadecanoic acid ( ¹²³ I) ( ¹²³ I-BMIPP). These radioactive iodine-labeled compounds can be synthesized by the non-radioactive iodine compound having, as a constituent element, a stable isotope of iodine that is substituted with a radioactive isotope of iodine by an iodine exchange reaction. In this specification, when simply referred to as "radioactive iodine", the meaning refers to iodine of a radioactive isotope, and in addition to ¹²³ I, ¹²⁴ I, ¹²⁵ I, and ¹³¹ I can be exemplified.

As shown in FIG. 1 , the reaction vessel 10 includes a main body portion 101 for accommodating a reaction solution, a connection port 102 with the return pipe 30 , and an inlet port 103 for introducing a reagent into the reaction vessel 10 . The connection port 102 is formed in the upper part of the reaction vessel 10 . The connection port 102 serves as both an outlet for discharging the vapor of the reaction solution from the main body 101 to the return pipe 30 and an inlet when the vapor cooled by the return pipe 30 turns into a liquid and returns to the main body 101 . A switchable valve 50 is attached to the input port 103 . By switching the valve 50, the inlet port 103 can be opened or closed. In addition, the reaction container 10 is connected to a vacuum pump via a line not shown. By using a switching valve provided in the line, the pressure of the reaction container 10 can be adjusted by opening the interior of the reaction container 10 to atmospheric pressure, decompressing the reaction container 10 with a vacuum pump, or forming a closed state.

Water is mentioned as a reaction solvent of an iodine exchange reaction. The radioactive iodine is preferably used in the form of radioactive sodium iodide. In addition, the iodine exchange reaction is preferably carried out in the presence of a catalyst, and as the catalyst, for example, copper sulfate can be used. In addition, a pH adjuster may be added to adjust the pH of the reaction solution. As this pH adjuster, formic acid can be used, for example.

The heating unit 20 is used to heat the reaction vessel 10 from below, and in the synthesis apparatus 1 of FIG. 1 , the heating unit 20 is configured to include a heat medium vessel 201 that accommodates a heat medium such as 1-acetoxy-2-ethoxyethane, and The heater 202 heats the heat medium contained in the heat medium container 201 . The reaction vessel 10 is provided in contact with the heat medium vessel 201 . More specifically, the heat medium container 201 is in contact with at least the bottom surface of the main body portion 101 . The heat of the heater 202 is transferred to the main body portion 101 through the heat medium in the heat medium container 201 , so that at least the bottom surface of the main body portion 101 is heated. In addition, when recirculating and using a heat medium such as 1-acetoxy-2-ethoxyethane, a condenser tube may be attached to the heat medium container 201 .

The return pipe 30 is used to return the reaction solution of the iodine exchange reaction to the reaction vessel 10 . The shape of the return pipe 30 is not particularly limited as long as it is a hollow elongated tubular shape. One end portion 30 a of the return pipe 30 is connected to the connection port 102 of the reaction vessel 10 .

As described above, the return pipe 30 is arranged above the position of the heating unit 20 . A part 301 of the reflux pipe 30 is arranged above the reaction vessel 10 in a spiral shape or a meandering shape. The return pipe 30 preferably extends in a direction away from the heating unit 20 from the one end portion 30 a as a starting point. Each part of the return pipe 30 is preferably arranged at a position higher than the connection port 102 or at the same height as the connection port 102 .

The return pipe 30 is preferably a flexible pipe.

The material of the reflux tube 30 is not particularly limited as long as it has resistance to the reaction solution of the iodine exchange reaction carried out in the synthesis apparatus 1 of the present invention, and for example, polytetrafluoroethylene (Teflon (registered trademark)) can be used.

The other end 30b of the return pipe 30 is connected to the trap 401 . As shown in FIG. 5 , the trap 401 is connected to an activated carbon trap (a container in which activated carbon is accommodated) 402 via a pipe 403 . The activated carbon trap 402 is open to the outside. The vapor containing radioactive iodine introduced into the activated carbon trap 402 from the side of the reaction vessel 10 passes through the activated carbon trap 402, whereby the radioactive iodine contained in the vapor is adsorbed by the activated carbon. Therefore, the vapor substantially free of radioactive iodine is released from the activated carbon trap 402 to the outside.

The length of the return pipe 30 is correspondingly sufficient to allow the vapor discharged from the connection port 102 to be cooled at room temperature. As for the vapor of the reaction solution discharged from the reaction vessel 10 to the return pipe 30, the vapor of the reaction solution is cooled in the return pipe 30 to become a liquid, and the liquid passes through the return pipe 30 and is returned (refluxed) by its own weight to the return pipe 30. Reaction vessel 10. This enables the iodine exchange reaction to proceed while refluxing.

In the present embodiment, since the recirculation pipe 30 has a swirling or meandering part 301, even if a sufficient length of the corresponding recirculation pipe 30 (particularly, a part 301) that can cool the vapor is ensured, the return pipe 30 can be recirculated. The tube 30 is configured in a space-saving manner. Moreover, since a part 301 is arrange|positioned at the upper position of the reaction container 10, the reaction solution which was cooled by the vapor|steam and returned to a liquid can be returned (recirculated) to the reaction container 10 from the reflux pipe 30 more reliably. By carrying out the iodine exchange reaction while maintaining such a reflux state, the amount of the reaction solution in the reaction vessel 10 can be sufficiently maintained, so that a good reaction yield (synthesis yield) of the radioiodine-labeled compound can be achieved.

In addition, since radioactive iodine generates radiation, it is preferable that at least the reaction vessel 10 is covered with the shielding body 60 from the viewpoint of radiation protection for the operator. In the example of FIG. 1 , the reaction vessel 10 , the heating unit 20 , etc. are arranged inside the shielding body 60 , and a part 301 of the return pipe 30 and the trap 401 are arranged outside the shielding body 60 .

It is preferable to synthesize|combine the radioactive iodine-labeled compound used as a medicine or a raw material of a medicine in a clean environment. Therefore, the reaction vessel 10 , the heating unit 20 , the shielding body 60 , the return pipe 30 , and the trap 401 of the synthesis apparatus 1 are preferably arranged in a clean bench. In this case, a part 301 of the return pipe 30 is preferably arranged along the top plate W of the clean table.

Here, as a clean table, a clean table of a type in which clean air is blown down from the top plate W is preferably used. In this case, since the part 301 of the return pipe 30 can be cooled by the air blown from the top plate W, the vapor of the reaction solution can be smoothly returned to the liquid inside the part 301 . That is, as a preferable example, the synthesis apparatus 1 includes a cooling unit (clean stage) that cools a part 301 of the recirculation pipe 30 .

Moreover, it is preferable to arrange|position the trap 401 and the activated carbon trap 402 above the heating part 20, and it is more preferable to arrange|position above the reaction container 10. Thereby, the iodine exchange reaction can be performed while maintaining the reflux state more reliably, and the reaction yield can be further improved.

When a part 301 of the recirculation pipe 30 is swirled, the part 301 is formed by winding the recirculation pipe 30 at least once, preferably twice or more, at a position above the reaction vessel 10 . That is, a part 301 is preferably wound twice or more.

The diameters (winding diameters) of the respective winding portions of the return pipe 30 in the part 301 may be the same or different from each other.

For example, the respective winding portions in the part 301 are bound to each other by being restrained by fasteners 70 (restraining members) ( FIG. 4 ) at a plurality of locations in the circumferential direction. Fasteners 70 are preferably rope-like fasteners. Each fastener 70 is wound around the plurality of winding portions at one location in the circumferential direction of the winding portion, and both ends of the fastener 70 are connected to each other, thereby restraining the plurality of winding portions. The connection between the both ends of the fastener 70 may be performed by entangling the both ends with each other, or may be performed by tying the both ends with each other. Fastener 70 may also be a strap. Furthermore, it is also preferable that the plurality of winding portions are bundled with the fasteners 70 and attached to the top plate W. As shown in FIG.

However, the present invention is not limited to this example, and a portion 301 may be formed in a spiral shape or a meander shape in advance.

The part 301 of the return pipe 30 is preferably formed by, for example, winding the return pipe 30 in a plane parallel to the surface of the top plate W of the clean table. That is, a part 301 of the return pipe 30 is preferably arranged horizontally (substantially horizontally), for example. In addition, the surface of the top plate W is arrange|positioned substantially horizontally.

More specifically, a part 301 of the reflux tube 30 is provided in a spiral shape above the reaction vessel 10, and a part 301 is wound twice or more in a plane parallel to the top plate surface (eg, the surface of the top plate W of the clean bench).

Here, a part 301 of the so-called return pipe 30 is arranged in a plane parallel to the top plate surface, and a part 301 may be arranged in a substantially vertical direction with respect to the top plate surface as long as it does not have a shape that spirally advances in the vertical direction like a spiral staircase. The situation in the upper parallel planes. It should be noted that a part 301 may be slightly inclined.

Moreover, it is also preferable that the height position of each part in the part 301 of the return pipe 30 rises monotonically as it moves away from the reaction container 10 side. That is, for example, the height position of each part in the part 301 preferably rises monotonically from the one end 301a which is the side end of the reaction vessel 10 of the part 301 toward the other end 301b which is the side end of the trap 401 of the part 301 .

As an example of this embodiment, as shown in FIG. 1 , the return pipe 30 includes a part 301 and a first intermediate part 302 (intermediate part) located between the part 301 and the reaction vessel 10 . The height position of each part in the first intermediate part 302 monotonically rises from one end of the first intermediate part 302 connected to the reaction vessel 10 (one end 30a of the return pipe 30 ) toward the part 301 (one end 301a toward the part 301 ). That is, it is preferable that the height position of each part in the 1st intermediate part 302 of the reflux pipe 30 also monotonously decreases toward the reaction container 10 side.

In this way, for example, the other end 30b of the return pipe 30 is connected to the trap 401, the trap 401 is connected to the activated carbon trap via the pipe, the activated carbon trap is open to the outside, and the trap 401 is arranged in the reaction vessel Above 10 , the reflux pipe 30 includes an intermediate portion (first intermediate portion 302 ) located between the reaction vessel 10 and a part 301 , and the height positions of the respective portions in the intermediate portion monotonically decrease toward the reaction vessel 10 side.

In addition, the return pipe 30 contains the 2nd intermediate part 303 located between the part 301 and the trap 401. As an example, the height position of each part in the second intermediate part 303 monotonically decreases from the other end 301b side of the part 301 toward the trap 401 side.

Hereinafter, an example of a method for synthesizing ¹²³ I-IMP using the synthesis apparatus 1 will be described with reference to FIG. 1 .

1-Acetoxy-2-ethoxyethane was put into the heat medium container 201 as a heat medium, and a condenser tube (not shown) was installed in the heat medium container 201 . Moreover, as the return pipe 30, a pipe made of polytetrafluoroethylene is used, and as shown in FIG.

Radioactive iodine (for example, ¹²³ I) can be produced by a nuclear reaction of the following formula (1) using a cyclotron. The following formula (1) shows a nuclear reaction in which ¹²⁴ Xe is irradiated with protons, and the generated ¹²³ Cs undergoes fission to obtain ¹²³ Xe, and further ¹²³ Xe undergoes fission to obtain ¹²³ I.

¹²⁴ Xe(p, 2n) ¹²³ Cs→ ¹²³ Xe→ ¹²³ I (1)

The radioactive iodine ( ¹²³ I) produced by the nuclear reaction of the above formula (1) is injected into the main body 101 of the reaction vessel 10 from the injection port 103 as an aqueous sodium hydroxide solution (about 5 to 10 mL).

Next, the radioactive iodine ( ¹²³ I) solution in the reaction vessel 10 is heated and evaporated under reduced pressure, and concentrated until the residual amount becomes about 1 mL.

Next, an aqueous solution (about 1 to 2 mL) of non-radioactive N-isopropyl-4-iodoamphetamine, copper sulfate, and formic acid was added to the main body portion 101 of the reaction vessel 10 from the inlet 103, and heated so that the heat The medium temperature was set to 150°C, and the iodine exchange reaction was carried out while refluxing for 40 minutes.

After cooling the reaction liquid after the iodine exchange reaction, post-treatment and purification were performed by liquid-liquid extraction using diethyl ether, hydrochloric acid and sodium hydroxide to obtain ¹²³ I-IMP.

<Variation>

As Modification 1, as shown in FIG. 2( a ), a part 301 of the return pipe 30 may be formed in a spiral shape whose winding diameter gradually decreases from one end 301 a to the other end 301 b.

Alternatively, a part 301 of the return pipe 30 may be formed in a spiral shape whose winding diameter gradually increases from one end 301a to the other end 301b.

That is, with respect to a part 301 of the return pipe 30, the winding diameter gradually decreases or expands from one end 301a of the part 301 to the other end 301b.

As Modification 2, as shown in FIG. 2( b ), a part 301 of the return pipe 30 may be formed in a meandering shape. In this case, it is preferable that the part 301 has a shape that meanders many times. That is, the part 301 preferably repeats the reciprocation to one side (for example, the upper side in FIG. 2( b )) and the side opposite to the one side (for example, the lower side in FIG. 2( b )). Make multiple shapes.

As Modification 3, as shown in FIG. 2( c ), a part 301 of the return pipe 30 may be formed in a meandering shape in which the meandering direction is changed in the middle.

Also in each of Modifications 1 to 3, it is preferable that the part 301 of the recirculation pipe 30 is arranged horizontally (substantially horizontally), or that the height position of each part in the part 301 of the recirculation pipe 30 increases monotonically as it moves away from the reaction vessel 10 side. .

In addition, the part 301 may be comprised so that both a spiral-shaped part and a meander-shaped part may be included.

The above-described embodiments and modifications include the following technical ideas.

(1) An apparatus for synthesizing a radioactive iodine-labeled compound, characterized in that it is used for synthesizing a radioactive iodine-labeled compound from a non-radioactive iodine compound through an iodine exchange reaction,

The synthesis device has:

A reaction vessel for carrying out the aforementioned iodine exchange reaction by refluxing the aforementioned non-radioactive iodine compound in a solution state and contacting it with radioactive iodine;

A heating section that heats the aforementioned reaction vessel from below; and

A tubular reflux pipe connected to the aforementioned reaction vessel for refluxing the reaction solution of the aforementioned iodine exchange reaction,

The return pipe is arranged above the position of the heating part,

A part of the said reflux pipe is arranged in a spiral shape or a meander shape above the said reaction vessel.

(2) The apparatus for synthesizing a radioactive iodine-labeled compound according to (1), wherein the part of the return pipe is arranged horizontally.

(3) The apparatus for synthesizing a radioactive iodine-labeled compound according to (1), wherein the height position of each part in the part of the reflux pipe monotonically increases as it moves away from the reaction container side.

(4) The apparatus for synthesizing a radioactive iodine-labeled compound according to any one of (1) to (3), wherein the return pipe includes the part and an intermediate part located between the part and the reaction vessel,

The height position of each part of the said intermediate part rises monotonically toward the said part from the one end part of the said intermediate part connected to the said reaction container.

(5) The apparatus for synthesizing a radioactive iodine-labeled compound according to any one of (1) to (4), which has a cooling unit that cools the part of the reflux tube.

Furthermore, the above-described embodiments and modifications include the following technical ideas.

<1> An apparatus for synthesizing a radioactive iodine-labeled compound, which is used for synthesizing a radioactive iodine-labeled compound from a non-radioactive iodine compound through an iodine exchange reaction,

The synthesis device has:

A reaction vessel for carrying out the aforementioned iodine exchange reaction by refluxing the aforementioned non-radioactive iodine compound in a solution state and contacting it with radioactive iodine;

A heating section that heats the aforementioned reaction vessel from below; and

A tubular reflux pipe connected to the aforementioned reaction vessel for refluxing the reaction solution of the aforementioned iodine exchange reaction,

The return pipe is arranged above the position of the heating part,

A part of the above-mentioned return pipe is arranged in a vortex above the above-mentioned reaction vessel,

The said part of the said return pipe is arrange|positioned horizontally.

<2> An apparatus for synthesizing a radioactive iodine-labeled compound, which is used for synthesizing a radioactive iodine-labeled compound from a non-radioactive iodine compound through an iodine exchange reaction,

The synthesis device has:

A reaction vessel for carrying out the aforementioned iodine exchange reaction by refluxing the aforementioned non-radioactive iodine compound in a solution state and contacting it with radioactive iodine;

A heating section that heats the aforementioned reaction vessel from below; and

A tubular reflux pipe connected to the aforementioned reaction vessel for refluxing the reaction solution of the aforementioned iodine exchange reaction,

The return pipe is arranged above the position of the heating part,

A part of the above-mentioned return pipe is arranged in a vortex above the above-mentioned reaction vessel,

The aforementioned part is wound twice or more in a plane parallel to the top plate surface.

<3> An apparatus for synthesizing a radioactive iodine-labeled compound, which is used for synthesizing a radioactive iodine-labeled compound from a non-radioactive iodine compound through an iodine exchange reaction,

The synthesis device has:

A reaction vessel for carrying out the aforementioned iodine exchange reaction by refluxing the aforementioned non-radioactive iodine compound in a solution state and contacting it with radioactive iodine;

A heating section that heats the aforementioned reaction vessel from below; and

A tubular reflux pipe connected to the aforementioned reaction vessel for refluxing the reaction solution of the aforementioned iodine exchange reaction,

The return pipe is arranged above the position of the heating part,

A part of the above-mentioned return pipe is arranged in a vortex above the above-mentioned reaction vessel,

The roll diameter of the aforementioned portion gradually decreases or expands from one end to the other end of the portion.

<4> The apparatus for synthesizing a radioactive iodine-labeled compound according to any one of <1> to <3>, wherein the return pipe includes the part and an intermediate part located between the part and the reaction vessel,

The height position of each part of the said intermediate part rises monotonically toward the said part from the one end part of the said intermediate part connected to the said reaction container.

<5> The apparatus for synthesizing a radioactive iodine-labeled compound according to any one of <1> to <4>, which has a cooling unit that cools the part of the reflux tube.

<6> The apparatus for synthesizing a radioactive iodine-labeled compound according to any one of <1> to <5>, wherein the part is wound twice or more, and the wound parts in the part pass each other in the circumferential direction Multiple parts on the upper are bound by fasteners.

<7> The apparatus for synthesizing a radioactive iodine-labeled compound according to any one of <1> to <6>, wherein the material of the return tube is polytetrafluoroethylene.

<8> The apparatus for synthesizing a radioactive iodine-labeled compound according to any one of <1> to <7>, wherein the other end of the return tube is connected to a trap,

The aforementioned trap is connected to the activated carbon trap via a pipe,

The aforementioned activated carbon trap is open to the outside,

The above-mentioned trap is arranged above the above-mentioned reaction vessel,

The aforementioned return pipe includes an intermediate portion between the aforementioned reaction vessel and the aforementioned portion,

The height position of each part in the said intermediate part monotonically falls toward the said reaction container side.

Example

¹²³ I-IMP was synthesized using the synthesis apparatus 1 of FIG. 1 and the synthesis apparatus 90 of the comparative example shown in FIG. 3, respectively, and the synthesis yields were compared.

(Example 1)

In Example 1, ¹²³ I-IMP was synthesized using the synthesis apparatus 1 described in the above-mentioned embodiment. The synthesis method of ¹²³ I-IMP using Synthesis Apparatus 1 was as described above, using about 150 GBq of radioactive iodine, and the result was 88.8±1.23% (mean±standard deviation, n=3), and even the lowest was 87.9% The synthetic yield of ¹²³ I-IMP was obtained.

(Comparative Example 1)

The synthesis apparatus 90 shown in FIG. 3 is different from the synthesis apparatus 1 in that a return pipe 901 is provided instead of the return pipe 30 and a trap 902 is provided instead of the trap 401 . The trap 902 is arranged at the same height as the heating unit 20 , that is, below the reaction vessel 10 . The return pipe 901 is the same as the return pipe 30 in that it is tubular. However, from one end 901 a (the end connected to the connection port 102 ) of the return pipe 901 toward the other end 901 b (the end connected to the trap 902 ), the height of the return pipe 901 first drops to the point where the return pipe 901 is connected to the heating unit 20 . The same height, then rises to the height above the reaction vessel 10 and descends again to the height of the trap 902 . In addition, the return pipe 901 does not have the swirling or meandering part 301 . For the synthesis method of ¹²³ I-IMP using the synthesis device 90, except that the synthesis device 90 was used instead of the synthesis device 1, as described above, about 150 GBq of radioactive iodine was used for synthesis, and the result was 78.9±3.33% (average Value ± standard deviation, n=3), the lowest was 75.2% synthesis yield.

From the above results, according to the present invention, a radioiodine-labeled compound based on an iodine exchange reaction can be obtained in a higher yield.

The present application claims priority based on Japanese Patent Application No. 2019-158364 for which it applied on August 30, 2019, and the entire disclosure thereof is incorporated herein.

Claims (8)

1. The synthetic apparatus of radioactive iodine-labeled compound, it is characterized in that, it is used for synthesizing radioactive iodine-labeled compound by iodine exchange reaction from non-radioactive iodine compound, The synthesis device has: a reaction vessel for carrying out the iodine exchange reaction by refluxing the non-radioactive iodine compound in solution and contacting it with radioactive iodine; a heating portion that heats the reaction vessel from below; and a tubular reflux pipe connected to the reaction vessel for refluxing the reaction solution of the iodine exchange reaction, The return pipe is arranged above the position of the heating part, A part of the reflux pipe is arranged in a vortex above the reaction vessel, The part of the return pipe is arranged horizontally. 2. The synthetic apparatus of radioactive iodine-labeled compound, it is characterized in that, it is used for synthesizing radioactive iodine-labeled compound by iodine exchange reaction from non-radioactive iodine compound, The synthesis device has: a reaction vessel for carrying out the iodine exchange reaction by refluxing the non-radioactive iodine compound in solution and contacting it with radioactive iodine; a heating portion that heats the reaction vessel from below; and a tubular reflux pipe connected to the reaction vessel for refluxing the reaction solution of the iodine exchange reaction, The return pipe is arranged above the position of the heating part, A part of the reflux pipe is arranged in a vortex above the reaction vessel, The part is wound twice or more in a plane parallel to the top plate surface. 3. The synthetic apparatus of radioactive iodine-labeled compound, it is characterized in that, it is used for synthesizing radioactive iodine-labeled compound by iodine exchange reaction from non-radioactive iodine compound, The synthesis device has: a reaction vessel for carrying out the iodine exchange reaction by refluxing the non-radioactive iodine compound in solution and contacting it with radioactive iodine; a heating portion that heats the reaction vessel from below; and a tubular reflux pipe connected to the reaction vessel for refluxing the reaction solution of the iodine exchange reaction, The return pipe is arranged above the position of the heating part, A part of the reflux pipe is arranged in a vortex above the reaction vessel, The roll diameter of the part gradually decreases or expands from one end to the other end of the part. 4. The apparatus for synthesizing a radioactive iodine-labeled compound according to any one of claims 1 to 3, wherein the return pipe includes the portion and an intermediate portion between the portion and the reaction vessel, The height position of each part of the said intermediate part rises monotonically toward the said part from one end part of the said intermediate part connected to the said reaction container. 5 . The apparatus for synthesizing a radioactive iodine-labeled compound according to claim 1 , which has a cooling unit that cools the part of the reflux pipe. 6 . 6 . The apparatus for synthesizing a radioactive iodine-labeled compound according to claim 1 , wherein the portion is wound twice or more, and the respective wound portions in the portion pass each other in the circumferential direction. 7 . The multiple parts of the device are bound by fasteners. 7 . The apparatus for synthesizing a radioactive iodine-labeled compound according to claim 1 , wherein the material of the return tube is polytetrafluoroethylene. 8 . 8. The apparatus for synthesizing a radioactive iodine-labeled compound according to any one of claims 1 to 3, wherein the other end of the return pipe is connected to a trap, The trap is connected to the activated carbon trap via a pipe, The activated carbon trap is open to the outside, The trap is arranged above the reaction vessel, the return pipe includes an intermediate portion between the reaction vessel and the portion, The height position of each of the intermediate portions monotonically decreases toward the reaction container side.

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