JP3133253B2 - FDG synthesizer that performs labeling and hydrolysis reactions on columns - Google Patents
FDG synthesizer that performs labeling and hydrolysis reactions on columnsInfo
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- JP3133253B2 JP3133253B2 JP08075536A JP7553696A JP3133253B2 JP 3133253 B2 JP3133253 B2 JP 3133253B2 JP 08075536 A JP08075536 A JP 08075536A JP 7553696 A JP7553696 A JP 7553696A JP 3133253 B2 JP3133253 B2 JP 3133253B2
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- fdg
- water
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Description
【０００１】[0001]
【発明の属する技術分野】この発明は、陽電子放射断層
画像(Positron Emission Tomography)（以下ＰＥＴとい
う）システムにおける標識化合物としてのＦＤＧを合成
する装置に関する。[0001] 1. Field of the Invention [0002] The present invention relates to an apparatus for synthesizing FDG as a labeling compound in a positron emission tomography (PET) system.
【０００２】[0002]
【従来の技術】医療分野において、人体内部の状態を画
像によって観察し診断する方法の一つとして、近年、陽
電子を出す物質を用いたＰＥＴシステムによる画像診断
法が注目されている。ＰＥＴシステムによる画像診断法
によれば、ガンなどの疾患の形態画像のみならず、体内
における血液や酸素の動きなどの機能画像を得ることが
でき、脳障害や心臓病などの診断に大きな威力が発揮さ
れる。2. Description of the Related Art In the medical field, as one of methods for observing and diagnosing the state of the inside of a human body by using an image, an image diagnosis method using a PET system using a substance that emits a positron has recently attracted attention. According to the diagnostic imaging method using the PET system, not only morphological images of diseases such as cancer, but also functional images such as movements of blood and oxygen in the body can be obtained, which has great power in diagnosing brain disorders and heart diseases. Be demonstrated.
【０００３】ＰＥＴシステムは、短半減期の放射性同位
元素を用いた画像診断システムであって、システムの概
略は次の通りである。 （１）サイクロトロンにおいてイオンを高エネルギーに
加速する。 （２）加速されたイオンを、反応容器であるターゲット
ボックスにおいて、ターゲットと呼ばれる材料に照射す
ることにより、放射性核種を生成する。 （３）上記放射性核種を原料とし、標識化合物合成装置
において、人体に投与できる放射性同位元素で標識され
た化合物を調製する。 （４）このようにして調製された標識化合物を人体内に
投与し、そして、スキャナによって人体内に取り込まれ
た上記標識化合物の分布を検出し、検出結果をコンピュ
ータにより画像化する。The PET system is a diagnostic imaging system using a short half-life radioisotope, and the outline of the system is as follows. (1) Accelerate ions to high energy in a cyclotron. (2) A radioactive nuclide is generated by irradiating accelerated ions to a material called a target in a target box as a reaction vessel. (3) Using the radionuclide as a raw material, a compound labeled with a radioisotope that can be administered to the human body is prepared in a labeled compound synthesizer. (4) The labeled compound thus prepared is administered into a human body, the distribution of the labeled compound taken into the human body is detected by a scanner, and the detection result is imaged by a computer.
【０００４】ＰＥＴシステム用の標識化合物としてＦＤ
Ｇ(Fluoro deoxy glucose)が知られている。ＦＤＧはグ
ルコースの一部を陽電子放出核種のＦ−18（半減期１１
９．７分）に置き換えた標識化合物であり、脳の機能や
悪性腫瘍の診断に使用されている。FD as a labeling compound for PET systems
G (Fluoro deoxy glucose) is known. FDG converts a portion of glucose to the positron emitting nuclide F-18 (half-life 11
9.7 minutes), and is used for brain function and diagnosis of malignant tumors.
【０００５】ＦＤＧの合成方法として、Hamacher等の方
法が知られている。この方法は、放射性同位元素である
Ｆ−18を化合物に結合させる標識反応の工程、および、
標識した中間生成物から保護基（通常アセチル基）を分
離する加水分解反応の工程からなっている。図１に従来
のＦＤＧの合成方法を示す。[0005] As a method for synthesizing FDG, Hamacher et al. Is known. This method comprises the steps of a labeling reaction for binding a radioisotope F-18 to a compound, and
It consists of a hydrolysis reaction step of separating a protecting group (usually an acetyl group) from the labeled intermediate product. FIG. 1 shows a conventional FDG synthesis method.
【０００６】図示しないサイクロトロンで加速したプロ
トン粒子をＯ−18水に照射し、ターゲットボックス内で
Ｆ−18マイナスイオンを製造する。このように製造し
た、Ｆ−18マイナスイオンが含まれているＯ−18水（以
下ターゲット水という）をターゲットボックス１から取
り出して、図１に示すように、ターゲット水中間容器２
に送る。次いで、ターゲット水中間容器２からターゲッ
ト水を陰イオン交換樹脂３に通して、Ｆ−18マイナスイ
オンを陰イオン交換樹脂でトラップし、Ｏ−18水を回収
容器４に回収する。[0006] O-18 water is irradiated with proton particles accelerated by a cyclotron (not shown) to produce F-18 negative ions in a target box. The thus produced O-18 water containing F-18 negative ions (hereinafter referred to as target water) is taken out of the target box 1 and, as shown in FIG.
Send to Next, the target water from the target water intermediate container 2 is passed through the anion exchange resin 3, the F-18 negative ions are trapped by the anion exchange resin, and the O-18 water is collected in the collection container 4.
【０００７】次いで、炭酸カリウム水溶液を容器５から
シリンジ６で吸い取り、そして、陰イオン交換樹脂３に
流して、Ｆ−18を抽出する。このように抽出されたＦ−
18は反応容器７へ送られる。次いで、Kryptofix222のア
セトニトリル溶液を容器８から反応容器７に送る。次い
で、反応容器７を加熱して容器内の水分を蒸発させる。
更に、容器内の水分が蒸発した後、アセトニトリルを容
器９からシリンジ１０で吸い取り、そして、反応容器７
に送り、再度、反応容器７を加熱して容器内の水分を充
分に蒸発させる。[0007] Next, the aqueous potassium carbonate solution is sucked from the container 5 with the syringe 6 and then flown into the anion exchange resin 3 to extract F-18. The F- extracted in this way
18 is sent to the reaction vessel 7. Next, an acetonitrile solution of Kryptofix 222 is sent from the container 8 to the reaction container 7. Next, the reaction vessel 7 is heated to evaporate the water in the vessel.
Further, after the water in the container evaporates, acetonitrile is sucked from the container 9 with the syringe 10, and
The reaction vessel 7 is heated again to sufficiently evaporate the water in the vessel.
【０００８】次いで、反応容器７の蒸発が充分に行われ
た後、反応基質である1,3,4,6-Tetra-0-acetyl-2-0-tri
fluoromethanesulfonyl-β-D-mannopyranose（以下トリ
フレートという）のアセトニトリル溶液を容器１１から
反応容器７に送り、そして、８０℃の温度で約５分間、
標識反応を行う。Then, after the reaction vessel 7 is sufficiently evaporated, the reaction substrate 1,3,4,6-Tetra-0-acetyl-2-0-tri
An acetonitrile solution of fluoromethanesulfonyl-β-D-mannopyranose (hereinafter referred to as triflate) is sent from the vessel 11 to the reaction vessel 7, and then at a temperature of 80 ° C. for about 5 minutes.
Perform labeling reaction.
【０００９】次いで、標識反応の終了後、水を容器１２
からシリンジ１３で吸い取って、反応容器７に送る。次
いで、反応容器７内の溶液を反応容器７からSepPakC-18
カートリッジ１４に通して、反応中間体である、溶液中
の4-acetyl-FDGを前記カートリッジ１４にトラップさ
せ、未反応のＦ−18およびKryptofix222を含む廃液を廃
液容器１５に送る。このように、4-acetyl-FDGは、未反
応のＦ−18およびKryptofix222から分離される。Then, after completion of the labeling reaction, water is added to the container 12.
Is sucked with a syringe 13 and sent to the reaction vessel 7. Next, the solution in the reaction vessel 7 is separated from the reaction vessel 7 by SepPakC-18.
Through the cartridge 14, 4-acetyl-FDG in the solution, which is a reaction intermediate, is trapped in the cartridge 14, and the waste liquid containing unreacted F-18 and Kryptofix 222 is sent to the waste liquid container 15. Thus, 4-acetyl-FDG is separated from unreacted F-18 and Kryptofix222.
【００１０】次いで、アセトニトリルを容器９からシリ
ンジ１０で吸い取り、精製した前記反応中間体を、カー
トリッジ１４から抽出して、再度、反応容器７に送る。
次いで、反応容器７を加熱して有機溶媒を蒸発させた
後、塩酸水溶液を容器１６からシリンジ１７で吸い取っ
て、反応容器７に加える。次いで、反応容器７を１３０
℃の温度で１０〜２０分間加熱して、加水分解反応を行
う。Next, acetonitrile is sucked from the container 9 with the syringe 10, and the purified reaction intermediate is extracted from the cartridge 14 and sent to the reaction container 7 again.
Next, after heating the reaction vessel 7 to evaporate the organic solvent, the aqueous hydrochloric acid solution is sucked from the vessel 16 with the syringe 17 and added to the reaction vessel 7. Next, the reaction vessel 7 is
The hydrolysis reaction is performed by heating at a temperature of 10C for 10 to 20 minutes.
【００１１】次いで、加水分解反応の終了後、水を容器
１２からシリンジで吸い取って、反応容器７に加える。
次いで、このように処理した反応容器７内の溶液をイオ
ン遅延樹脂カラム１８、精製カラム１９に順次通して、
合成されたＦＤＧをＦＤＧ容器２０に収容する（以下、
先行技術１という）。Then, after the completion of the hydrolysis reaction, water is sucked from the container 12 with a syringe and added to the reaction container 7.
Next, the solution in the reaction vessel 7 thus treated is sequentially passed through the ion delay resin column 18 and the purification column 19,
The synthesized FDG is stored in the FDG container 20 (hereinafter, referred to as FDG container 20).
Prior art 1).
【００１２】先行技術１において、イオン遅延樹脂の代
わりに水酸化ナトリウム水溶液を使用して、中和反応に
よって塩酸を除去する以外は、先行技術１と同一プロセ
スで処理して、合成されたＦＤＧを得る（以下、先行技
術２という）。In the prior art 1, the FDG synthesized was processed by the same process as in the prior art 1 except that an aqueous solution of sodium hydroxide was used instead of the ion-delay resin to remove hydrochloric acid by a neutralization reaction. (Hereinafter referred to as Prior Art 2).
【００１３】先行技術１および２においては、標識反応
時にKryptofix222またはテトラブチルアンモニウム炭酸
水素塩（ＴＢＡＨＣＯ3 ）の相間移動触媒を添加するの
で、添加したこれ等相間移動触媒を除去するプロセスが
必要になる。更に、上述した相間移動触媒を使用するた
め、水分を蒸発乾固によって完全に除去する必要があ
り、水分の除去に時間がかかるという問題点がある。更
に、Ｏ−18水の回収のために、陰イオン交換樹脂を使用
する特別のプロセスが必要であり、ＦＤＧ合成操作プロ
セスが複雑になるという問題点がある。Ｆ−18の半減期
は約２時間であり、合成に時間がかかり過ぎるとＦＤＧ
の収量を低下させるという問題点がある。In the prior arts 1 and 2, a phase transfer catalyst of Kryptofix222 or tetrabutylammonium bicarbonate (TBAHCO 3 ) is added at the time of the labeling reaction, so a process for removing the added phase transfer catalyst is required. . Furthermore, since the above-mentioned phase transfer catalyst is used, it is necessary to completely remove water by evaporation to dryness, and there is a problem that it takes time to remove water. Furthermore, a special process using an anion exchange resin is required for the recovery of O-18 water, and there is a problem that the process of synthesizing the FDG becomes complicated. The half-life of F-18 is about 2 hours, and if synthesis takes too long, FDG
There is a problem that the yield of coconut is reduced.
【００１４】更に、加水分解時に塩酸水溶液または水酸
化ナトリウム水溶液を収容する容器が必要であり、そし
て、塩酸水溶液または水酸化ナトリウム水溶液を除去す
るためのイオン遅延樹脂または中和用の試薬が必要であ
る。更に、イオン遅延樹脂を使用するときは、イオン遅
延樹脂中に細菌が繁殖し易く、樹脂中に細菌毒素（パイ
ロジェン）が混入し易いため、使用前に充分にイオン遅
延樹脂を洗浄する必要がある。更に、中和反応を利用す
るときは、加水分解反応中に塩酸または水酸化ナトリウ
ムが失われるので、正確に等量の反応を行わせることが
困難であり、そのためにリン酸バッフアー等を用いる
と、ＦＤＧ中に不純物のリン酸等が混入してしまうとい
う問題点がある。Further, a container for accommodating an aqueous hydrochloric acid solution or an aqueous sodium hydroxide solution during the hydrolysis is required, and an ion retarding resin or a neutralizing reagent for removing the aqueous hydrochloric acid solution or the aqueous sodium hydroxide solution is required. is there. Furthermore, when using an ion-delay resin, it is necessary to sufficiently wash the ion-delay resin before use, since bacteria easily propagate in the ion-delay resin and bacterial toxins (pyrogen) are easily mixed in the resin. . Furthermore, when using a neutralization reaction, hydrochloric acid or sodium hydroxide is lost during the hydrolysis reaction, so that it is difficult to carry out an exact equivalent amount of the reaction. However, there is a problem that phosphoric acid and the like as impurities are mixed in the FDG.
【００１５】[0015]
【発明が解決しようとする課題】従って、この発明の目
的は、先行技術の有する上述した問題点を解決するため
になされたものであって、ＦＤＧ合成装置におけるプロ
セスが簡略化され、合成収率が向上し、そして、合成時
間が短縮化されたＦＤＧ合成装置を提供することにあ
る。SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to solve the above-mentioned problems in the prior art, and the process in the FDG synthesis apparatus is simplified, and the synthesis yield is improved. It is an object of the present invention to provide an FDG synthesizing apparatus in which the synthesis time is improved and the synthesizing time is shortened.
【００１６】[0016]
【課題を解決するための手段】本発明者等は、上述した
問題を解決すべく鋭意研究を重ねた。その結果、標識反
応を行う従来の反応容器の代わりに、ポリスチレン樹脂
に、ホスホニウム塩またはピリジニウム塩を固定化する
ことからなる固定化相間移動触媒樹脂を充填したカラム
を使用し、そして、加水分解反応容器の代わりに、陽イ
オン交換樹脂を充填したカラムを使用することにより、
ＦＤＧ合成プロセスが簡略化され、合成収率が向上し、
そして、合成時間が短縮化されたＦＤＧ合成装置を得る
ことができることを知見した。Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems. As a result, instead of a conventional reaction vessel for performing a labeling reaction, a column packed with an immobilized phase transfer catalyst resin consisting of immobilizing a phosphonium salt or a pyridinium salt on a polystyrene resin is used, and a hydrolysis reaction is performed. By using a column packed with a cation exchange resin instead of a container,
The FDG synthesis process is simplified, the synthesis yield is improved,
And it discovered that the FDG synthesizer with which synthesis time was shortened could be obtained.
【００１７】本発明の標識反応および加水分解反応をカ
ラムで行うＦＤＧ合成装置は、上記知見に基ずきなされ
たものであって、Ｆ−１８マイナスイオンが含まれてい
るＯ−１８水に含まれているＦ−18マイナスイオンをト
ラップし、次いで前記Ｆ−18マイナスイオンと１，３，
４，６−テトラ−０−アセチル−２−０−トリフルオロ
メタンスルホニル−β−Ｄ−マンノピラノースとの間で
標識反応を行うための、固定化相間移動触媒樹脂を充填
したカラムからなる標識反応用樹脂カラム、および、前
記標識反応によって得られた中間生成物をＨ＋ 型に調
製した陽イオン交換樹脂に接触させ、加水分解反応を行
うための、陽イオン交換樹脂カラムからなることを特徴
とする、標識反応および加水分解反応をカラムで行うこ
とを特徴とするものである。The FDG synthesizer of the present invention for performing a labeling reaction and a hydrolysis reaction in a column is based on the above findings, and contains F-18 negative ions.
Trap the F-18 negative ions contained in the O-18 water, and then combine the F-18 negative ions with 1,3,3.
4,6-tetra-0-acetyl-2-0-trifluoro
A resin column for labeling reaction comprising a column filled with an immobilized phase transfer catalyst resin for performing a labeling reaction with methanesulfonyl-β-D-mannopyranose , and an intermediate product obtained by the labeling reaction Contacting the product with a cation exchange resin prepared in H + form, and performing a hydrolysis reaction, comprising a cation exchange resin column, wherein the labeling reaction and the hydrolysis reaction are performed in a column. Is what you do.
【００１８】[0018]
【発明の実施の形態】次に、この発明を、図面を参照し
ながら説明する。図２は、この発明のＦＤＧ合成装置の
１実施態様を示す概略説明図である。本発明の装置は、
Ｆ−18マイナスイオンをトラップし、次いで水分を除去
し、次いで前記Ｆ−18マイナスイオンとトリフレートと
の間で標識反応を行うための、標識反応用樹脂カラム、
前記標識反応によって得られた中間生成物をＨ+ 型に調
整した陽イオン交換樹脂に接触させ、加熱して加水分解
反応を行うための、陽イオン交換樹脂カラムおよび精製
するための精製カラムからなっている。図２において、
５は樹脂カラムであり、１５は陽イオン交換樹脂カラム
であり、２０は精製カラムである。樹脂カラム５は、ポ
リスチレン樹脂にホスホニウム塩またはピリジニウム塩
を固定化した、即ち、固定化ホスホニウム塩または固定
化ピリジニウム塩からなる固定化相間移動触媒樹脂を充
填したカラムからなっている。樹脂カラム５では、ター
ゲット水を通過させて、ターゲット水に含まれているＦ
−18マイナスイオンをトラップし、次いで、アセトニト
リル溶液を通過させて、カラム内を乾燥させ、そして、
次いで、トリフレート溶液を通過させて、トラップされ
たＦ−18マイナスイオンとトリフレートとの間で標識反
応が行われる。Next, the present invention will be described with reference to the drawings. FIG. 2 is a schematic explanatory view showing one embodiment of the FDG synthesizing apparatus of the present invention. The device of the present invention
A resin column for labeling reaction for trapping F-18 negative ions, then removing water, and then performing a labeling reaction between the F-18 negative ions and triflate;
The intermediate product obtained by the labeling reaction is brought into contact with a cation exchange resin adjusted to H + type, and heated to perform a hydrolysis reaction, comprising a cation exchange resin column and a purification column for purification. ing. In FIG.
5 is a resin column, 15 is a cation exchange resin column, and 20 is a purification column. The resin column 5 is a column in which a phosphonium salt or a pyridinium salt is immobilized on a polystyrene resin, that is, a column filled with an immobilized phase transfer catalyst resin composed of an immobilized phosphonium salt or an immobilized pyridinium salt. In the resin column 5, the target water is allowed to pass through and the F contained in the target water is removed.
Trap -18 negative ions, then pass through an acetonitrile solution, dry the column, and
Next, a labeling reaction is performed between the trapped F-18 anion and triflate by passing through a triflate solution.
【００１９】標識反応用樹脂カラム５を通過し、トラッ
プされたＦ−18マイナスイオンと分離されたＯ−18水
は、バルブ１０操作によって、回収容器６に回収され、
アセトニトリル溶液等は、バルブ操作によって、廃液容
器１１に回収される。上述したように、樹脂カラムにお
いて、Ｆ−18マイナスイオンがトラップされ、そして、
次いで標識反応が行われるので、Ｏ−18水の回収のため
の別個のプロセスが不要になり、標識反応を阻害する水
分の除去が、反応容器をカラム化することによって、有
機溶媒をカラムに通すだけで、カラム内の水分除去が可
能になる。更に、触媒が樹脂に固定化されているため、
触媒を分離除去する別個のプロセスが不要になると共
に、標識反応率が向上する。The O-18 water that has passed through the labeling reaction resin column 5 and has been separated from the trapped F-18 negative ions is recovered in the recovery container 6 by operating the valve 10.
The acetonitrile solution and the like are collected in the waste liquid container 11 by operating a valve. As described above, in the resin column, F-18 negative ions are trapped, and
The labeling reaction is then performed, eliminating the need for a separate process for the recovery of O-18 water, and removing the water that inhibits the labeling reaction by passing the organic solvent through the column by columnizing the reaction vessel. Alone, it is possible to remove water from the column. Furthermore, since the catalyst is fixed to the resin,
A separate process for separating and removing the catalyst is not required, and the labeling reaction rate is improved.
【００２０】陽イオン交換樹脂カラム１５においては、
標識反応用樹脂カラム５で標識反応によって標識された
中間生成物から保護基（通常アセチル基）を分離する加
水分解反応のプロセスが行われる。即ち、Ｆ−18マイナ
スイオンがトラップされた樹脂カラム５にトリフレート
溶液を通過させ、標識反応が行われた溶液をＨ+ 型に調
製した陽イオン交換樹脂に接触させ、同時にアセトニト
リルを蒸発させ、次いで１３０℃の温度で１０〜１５分
間加熱して、加水分解反応を行う。従って、加水分解反
応時に、塩酸水溶液または水酸化ナトリウム水溶液が不
要となり、反応容器が要らなくなる。In the cation exchange resin column 15,
A hydrolysis reaction process for separating a protecting group (usually an acetyl group) from an intermediate product labeled by the labeling reaction in the labeling reaction resin column 5 is performed. That is, the triflate solution is passed through a resin column 5 in which F-18 negative ions are trapped, the solution subjected to the labeling reaction is brought into contact with a cation exchange resin prepared in H + type, and acetonitrile is evaporated at the same time. Next, the mixture is heated at a temperature of 130 ° C. for 10 to 15 minutes to perform a hydrolysis reaction. Therefore, during the hydrolysis reaction, an aqueous hydrochloric acid solution or an aqueous sodium hydroxide solution becomes unnecessary, and a reaction vessel becomes unnecessary.
【００２１】加水分解反応を行った後、無菌水を加えた
て、精製カラム２０を通過させて、ＦＤＧを合成する。
即ち、加水分解後は、水で流し出すだけの簡単な操作で
ＦＤＧを水溶液中に得ることができる。After the hydrolysis reaction, sterile water is added, and the mixture is passed through a purification column 20 to synthesize FDG.
That is, after the hydrolysis, FDG can be obtained in an aqueous solution by a simple operation of flowing out with water.
【００２２】ターゲット水容器２、アセトニトリル容器
８、トリフレ−ト容器１２が、シリンジポンプ３、７、
および、３方バルブ４、９、１３を介して、標識反応用
樹脂カラム５に連絡されている。更に、標識反応用樹脂
カラム５には、Ｏ−18水回収容器６、廃液容器１１が連
絡されている。陽イオン交換樹脂カラム１５は、標識反
応用樹脂カラム５と連絡されており、そして、無菌水容
器１６と、シリンジポンプ１７、および、３方バルブ１
８を介して連絡されている。更に、陽イオン交換樹脂カ
ラム１５は、３方バルブ１９を介して精製カラム２０と
連絡されている。The target water container 2, the acetonitrile container 8, and the triflate container 12 include the syringe pumps 3, 7,
And, it is connected to the resin column 5 for labeling reaction via the three-way valves 4, 9 and 13. Further, an O-18 water recovery container 6 and a waste liquid container 11 are connected to the labeling reaction resin column 5. The cation exchange resin column 15 is in communication with the labeling reaction resin column 5, and includes a sterile water container 16, a syringe pump 17, and a three-way valve 1.
8 has been contacted. Further, the cation exchange resin column 15 is connected to a purification column 20 via a three-way valve 19.
【００２３】[0023]
【実施例】本発明の装置を実施例によって、詳細に説明
する。本発明の装置において使用する標識反応用樹脂カ
ラムは、エタノールと水の混合溶媒に、１００〜２００
メッシュの樹脂を混ぜ合わせてスラリー状としたもの
を、内径２ｍｍ長さ５ｃｍの円筒形の、例えば、ステン
レス製のカラムに充填することによって形成されてい
る。更に、本発明の装置において使用する陽イオン交換
樹脂カラムは、Ｈ+ 型に調製した陽イオン交換樹脂を内
径１２ｍｍ長さ４ｃｍの円筒形のカラムに充填すること
によって形成されている。図２に示すように、ターゲッ
トボックス１から、ターゲット水、即ち、照射済みのＦ
−18マイナスイオンを含むＯ−18水をターゲット水容器
２に送液した。ターゲット水容器２からシリンジポンプ
３にターゲット水を吸い込み、３方バルブ４を切り換え
て、ターゲット水を樹脂カラム５に送り、Ｆ−18を樹脂
中にトラップすると同時に、Ｏ−18水を分離して回収容
器６に送った。次にシリンジポンプ７でアセトニトリル
容器８に入っているアセトニトリルを吸い込み、３方バ
ルブ９、３方バルブ１０を切り替えて樹脂カラム５にア
セトニトリルを流して、樹脂カラム５内を乾燥させ、ア
セトニトリルは廃液容器１１に流した。DESCRIPTION OF THE PREFERRED EMBODIMENTS The apparatus of the present invention will be described in detail with reference to embodiments. The resin column for labeling reaction used in the apparatus of the present invention is prepared by adding 100 to 200 to a mixed solvent of ethanol and water.
The slurry is formed by mixing a mesh resin into a slurry, and filling the slurry into a cylindrical, for example, stainless steel column having an inner diameter of 2 mm and a length of 5 cm. Further, the cation exchange resin column used in the apparatus of the present invention is formed by packing a cation exchange resin prepared in H + type into a cylindrical column having an inner diameter of 12 mm and a length of 4 cm. As shown in FIG. 2, target water, that is, irradiated F
O-18 water containing -18 negative ions was sent to the target water container 2. The target water is sucked into the syringe pump 3 from the target water container 2, the three-way valve 4 is switched, the target water is sent to the resin column 5, and F-18 is trapped in the resin, and at the same time, O-18 water is separated. It was sent to the collection container 6. Next, the acetonitrile contained in the acetonitrile container 8 is sucked by the syringe pump 7, the three-way valve 9, the three-way valve 10 is switched, the acetonitrile is caused to flow through the resin column 5, and the inside of the resin column 5 is dried. 11 was poured.
【００２４】次いで、トリフレート容器１２からシリン
ジポンプ７でトリフレート溶液を吸い取り、３方バルブ
１３、３方バルブ１４を切り替えてトリフレート溶液を
樹脂カラム５に流して樹脂カラム内で標識反応を行い、
中間生成物を、陽イオン交換樹脂カラム１５に送液し
た。同時にアセトニトリルを蒸発させ、次いで、１３０
℃の温度で１０から１５分間加熱して、加水分解反応を
行った。Next, the triflate solution is sucked from the triflate container 12 by the syringe pump 7 and the three-way valve 13 and the three-way valve 14 are switched to flow the triflate solution to the resin column 5 to carry out a labeling reaction in the resin column. ,
The intermediate product was sent to the cation exchange resin column 15. Simultaneously evaporate the acetonitrile, then 130
The hydrolysis reaction was carried out by heating at a temperature of 10 ° C. for 10 to 15 minutes.
【００２５】加水分解反応後、無菌水容器１６から３方
バルブ１８を切り替え、無菌水をシリンジポンプ１７に
吸い込み、陽イオン交換樹脂カラム１５に送り、３方バ
ルブ１９を切り替えて反応溶液を精製カラム２０に通
し、ＦＤＧを得た。本発明のＦＤＧ合成装置によるＦＤ
Ｇ合成結果を、表１に示す。After the hydrolysis reaction, the three-way valve 18 is switched from the sterile water container 16, the sterile water is sucked into the syringe pump 17, sent to the cation exchange resin column 15, and the three-way valve 19 is switched so that the reaction solution is purified. 20 to obtain FDG. FD by FDG synthesis device of the present invention
Table 1 shows the results of G synthesis.
【００２６】[0026]
【表１】 [Table 1]
【００２７】表１から明らかなように、本発明のＦＤＧ
装置によると、合成プロセスが先行技術の約半分のプロ
セスに簡略化でき、同時に、合成に要する時間が大幅に
短縮された。As is clear from Table 1, the FDG of the present invention
According to the apparatus, the synthesis process can be simplified to about half that of the prior art, and at the same time, the time required for the synthesis is greatly reduced.
【００２８】[0028]
【発明の効果】本発明の装置によると、ＦＤＧ合成装置
におけるプロセスが簡略化され、合成収率が向上し、そ
して、合成時間が短縮化されたＦＤＧ合成装置を提供す
ることができ、工業上有用な効果がもたらされる。According to the apparatus of the present invention, it is possible to provide an FDG synthesis apparatus in which the process in the FDG synthesis apparatus is simplified, the synthesis yield is improved, and the synthesis time is shortened. A useful effect is provided.
【図１】図１は、先行技術のＦＤＧ合成装置を示す概略
説明図である。FIG. 1 is a schematic explanatory view showing a conventional FDG synthesizing apparatus.
【図２】図２は、この発明のＦＤＧ合成装置の１実施態
様を示す概略説明図である。FIG. 2 is a schematic explanatory view showing one embodiment of an FDG synthesizing apparatus according to the present invention.
１ ターゲットボックス ２ ターゲット水容器 ３ シリンジポンプ ４ ３方バルブ ５ 標識反応用樹脂カラム ６ 回収容器 ７ シリンジポンプ ８ アセトニトリル容器 ９ ３方バルブ １０ ３方バルブ １１ 廃液容器 １２ トリフレート容器 １３ ３方バルブ １４ ３方バルブ １５ 陽イオン交換樹脂カラム １６ 無菌水容器 １７ シリンジポンプ １８ ３方バルブ １９ ３方バルブ ２０ 精製カラム DESCRIPTION OF SYMBOLS 1 Target box 2 Target water container 3 Syringe pump 4 Three-way valve 5 Resin column for labeling reaction 6 Recovery container 7 Syringe pump 8 Acetonitrile container 9 Three-way valve 10 Three-way valve 11 Waste liquid container 12 Triflate container 13 Three-way valve 14 3 One-way valve 15 Cation exchange resin column 16 Sterile water container 17 Syringe pump 18 Three-way valve 19 Three-way valve 20 Purification column
フロントページの続き (56)参考文献 特開 昭55−143999（ＪＰ，Ａ) 特表 平７−507813（ＪＰ，Ａ) Ｎｕｃｌ．Ｍｅｄ．Ｂｉｏｌ．，Ｖｏ ｌ．17，Ｎｏ．３（1990）ｐ．273−279 (58)調査した分野(Int.Cl.7，ＤＢ名) C07H 5/02 C07B 59/00 Continuation of the front page (56) References JP-A-55-143999 (JP, A) Table 7-7-507813 (JP, A) Nucl. Med. Biol. , Vol. 17, No. 3 (1990) p. 273-279 (58) Field surveyed (Int. Cl. 7 , DB name) C07H 5/02 C07B 59/00
Claims (1)
Ｏ−１８水に含まれているＦ−18マイナスイオンをトラ
ップし、次いで前記Ｆ−18マイナスイオンと１，３，
４，６−テトラ−０−アセチル−２−０−トリフルオロ
メタンスルホニル−β−Ｄ−マンノピラノースとの間で
標識反応を行うための、固定化相間移動触媒樹脂を充填
したカラムからなる標識反応用樹脂カラム、および、前
記標識反応によって得られた中間生成物をＨ＋ 型に調
製した陽イオン交換樹脂に接触させ、加水分解反応を行
うための、陽イオン交換樹脂カラムからなることを特徴
とする、標識反応および加水分解反応をカラムで行うフ
ルオロデオキシグルコース合成装置。1. F-18 negative ions are contained
The F-18 negative ions contained in the O-18 water are trapped, and then the F-18 negative ions are combined with 1,3,
4,6-tetra-0-acetyl-2-0-trifluoro
A resin column for labeling reaction comprising a column filled with an immobilized phase transfer catalyst resin for performing a labeling reaction with methanesulfonyl-β-D-mannopyranose , and an intermediate product obtained by the labeling reaction object is brought into contact with the cation-exchange resin prepared in H + form, for carrying out the hydrolysis reaction, characterized by comprising the cation exchange resin column, perform labeling reaction and hydrolysis reaction column off
Luodeoxyglucose synthesizer.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP08075536A JP3133253B2 (en) | 1996-03-29 | 1996-03-29 | FDG synthesizer that performs labeling and hydrolysis reactions on columns |
| US08/824,566 US5932178A (en) | 1996-03-29 | 1997-03-26 | FDG synthesizer using columns |
| EP97105302A EP0798307B1 (en) | 1996-03-29 | 1997-03-27 | Fluoro-deoxyglucose synthesizer using columns |
| EP01115180A EP1134228B1 (en) | 1996-03-29 | 1997-03-27 | Fluoro-deoxyglucose synthesizer using columns |
| DE69719831T DE69719831T2 (en) | 1996-03-29 | 1997-03-27 | Fluorine-deoxy-glucose synthesizer using columns |
| DE69719576T DE69719576T2 (en) | 1996-03-29 | 1997-03-27 | Fluoro-deoxy-glucose synthesizer using columns |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP08075536A JP3133253B2 (en) | 1996-03-29 | 1996-03-29 | FDG synthesizer that performs labeling and hydrolysis reactions on columns |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH09263594A JPH09263594A (en) | 1997-10-07 |
| JP3133253B2 true JP3133253B2 (en) | 2001-02-05 |
Family
ID=13579042
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP08075536A Expired - Lifetime JP3133253B2 (en) | 1996-03-29 | 1996-03-29 | FDG synthesizer that performs labeling and hydrolysis reactions on columns |
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| Country | Link |
|---|---|
| JP (1) | JP3133253B2 (en) |
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|---|---|---|---|---|
| ES2347535T3 (en) * | 2002-11-05 | 2010-11-02 | Ion Beam Applications S.A. | STABILIZATION OF 2-FLUORO-2-DESOXI-D-GLUCOSE COMPOSITIONS MARKED WITH ISOTOPO 18F WITH ETHANOL. |
| WO2005044758A1 (en) * | 2003-11-11 | 2005-05-19 | Nihon Medi-Physics Co., Ltd. | Process for producing radioactive-fluorine-labeled compound |
| EP2386562A4 (en) * | 2009-01-07 | 2012-08-08 | Nat Inst Of Advanced Ind Scien | Halogen-substituted saccharide, method for producing same, reaction composition of same and device for producing same |
| JP2010106041A (en) * | 2010-01-14 | 2010-05-13 | Ion Beam Applications Sa | Stabilization of radiopharmaceutical labeled with 18f |
| JP5835801B2 (en) * | 2010-02-12 | 2015-12-24 | 国立大学法人東京工業大学 | Method for producing 18F-labeled compound and polymer compound used in the method |
| KR101221483B1 (en) * | 2011-05-13 | 2013-01-16 | 서강대학교산학협력단 | Apparatus and method for synthesis of F-18 labelled radiopharmaceuticals |
-
1996
- 1996-03-29 JP JP08075536A patent/JP3133253B2/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| Ｎｕｃｌ．Ｍｅｄ．Ｂｉｏｌ．，Ｖｏｌ．１７，Ｎｏ．３（１９９０）ｐ．２７３−２７９ |
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