JPH0853475A - Phospholipid compound containing radioactive iodine-labeled boron - Google Patents
Phospholipid compound containing radioactive iodine-labeled boronInfo
- Publication number
- JPH0853475A JPH0853475A JP6209325A JP20932594A JPH0853475A JP H0853475 A JPH0853475 A JP H0853475A JP 6209325 A JP6209325 A JP 6209325A JP 20932594 A JP20932594 A JP 20932594A JP H0853475 A JPH0853475 A JP H0853475A
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- Prior art keywords
- boron
- compound
- tumor
- formula
- radioactive iodine
- Prior art date
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、癌の診断並びに治療に
好適なホウ素含有リン脂質化合物に関し、更に詳細に
は、放射性ヨウ素で標識されたことにより、腫瘍の局存
を画像診断することができ、更に中性子捕捉療法（ＢＮ
ＣＴ）のための薬剤としても用いることのできるホウ素
含有リン脂質化合物に関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a boron-containing phospholipid compound suitable for cancer diagnosis and treatment, and more specifically, it is possible to perform diagnostic imaging of tumor localization by labeling with radioactive iodine. Neutron capture therapy (BN
It also relates to boron-containing phospholipid compounds that can also be used as agents for CT).
【０００２】[0002]
【従来の技術】近年、癌に対する種々の診断及び治療方
法が開発され、なかでも放射性アイソトープを利用する
診断及び治療方法の進歩はめざましい。 このうち、10
Ｂを含む化合物（10Ｂキャリア）を癌細胞に取りこませ
た後、低エネルギーの熱中性子線を照射し、次式のよう
な核反応を生体内で起こさせることによって組織中の癌
細胞を破壊する、いわゆるホウ素中性子捕捉療法（ＢＮ
ＣＴ）は理想的且つ幅広い癌治療法として大いに期待さ
れている。2. Description of the Related Art In recent years, various diagnostic and therapeutic methods for cancer have been developed, and among them, the progress of diagnostic and therapeutic methods utilizing radioactive isotopes is remarkable. Of these, 10
After incorporating a compound containing B ( 10 B carrier) into cancer cells, it is irradiated with a low-energy thermal neutron beam to cause a nuclear reaction as shown in the following formula to occur in vivo, thereby causing cancer cells in the tissue to Destruction, so-called boron neutron capture therapy (BN
CT) is highly expected as an ideal and widespread cancer treatment method.
【０００３】10 Ｂ＋0 1ｎ → 7Ｌｉ＋ 2 4Ｈｅ＋２.４ＭｅＶ このＢＮＣＴを行う際には癌組織への10Ｂの高い取り込
みがその治療効果を高める上できわめて重要であり、現
在多くのホウ素化合物の中から、腫瘍への取り込みが高
く、かつ多くのホウ素原子を含む化合物としてメルカプ
トウンデカヒドロドデカボレート（ＢＳＨ）やバラボロ
ノフェニルアラニン（ＢＰＡ）といった化合物が用いら
れてきたが、その腫瘍への取り込みの程度及び腫瘍選択
性にはなお問題があった。 10 B + 0 1 n → 7 Li + 2 4 He + 2.4 MeV In carrying out this BNCT, high uptake of 10 B into cancer tissue is extremely important for enhancing its therapeutic effect, and many boron compounds are presently used. Among these, compounds such as mercaptoundecahydrododecaborate (BSH) and baraboronophenylalanine (BPA), which have high uptake into tumor and contain many boron atoms, have been used. There were still problems with the degree of uptake and tumor selectivity.
【０００４】一方、ＢＮＣＴ法による中性子線照射を施
行する際には腫瘍部位の確定とホウ素原子の腫瘍部位へ
の取り込み量を正確に知る必要があるが、従来、取り込
み量の算出に当たってはホウ素化合物を投与した後、血
液中のホウ素（Ｂ−10）濃度を放射化測定（prompt gam
ma 法）によって測定し、腫瘍へのホウ素（Ｂ−10）濃
度を推定する方法がとられ、また実際との誤差を補正す
るためにあらかじめ腫瘍組織に挿入された金線を中性子
照射中に取り出し、その放射化測定で中性子照射が最終
的に決定されるという、きわめて煩雑且つ正確さの欠け
る方法がとられてきた。On the other hand, when performing neutron irradiation by the BNCT method, it is necessary to determine the tumor site and accurately know the uptake amount of boron atoms into the tumor site. Conventionally, boron compounds have been used to calculate the uptake amount. After administration, the concentration of boron (B-10) in blood was measured by activation (prompt gam
Ma method) to estimate the boron (B-10) concentration in the tumor, and the gold wire previously inserted into the tumor tissue was taken out during neutron irradiation to correct the error from the actual one. , A very complicated and inaccurate method has been taken in which the neutron irradiation is finally determined by the activation measurement.
【０００５】[0005]
【発明が解決しようとする課題】従って、癌の存在を正
確に診断し、また、治療をより有効に実施するために
は、腫瘍に対して高い親和性と選択性をもち、かつ、標
識能を有する化合物の開発が必須であり、特に有効なホ
ウ素中性子捕捉療法（ＢＮＣＴ）を実施するためには上
記の他、正常組織に対する損傷を最小限にすることと腫
瘍部位への薬剤濃度の絶対値が高いことが要求されてお
り、このような要求を満足する化合物の提供が強く求め
られていた。Therefore, in order to accurately diagnose the presence of cancer and to carry out the treatment more effectively, it has a high affinity and selectivity for tumors and a labeling ability. In order to carry out boron neutron capture therapy (BNCT) that is particularly effective, it is essential to develop a compound having the following: In addition to the above, the damage to normal tissues should be minimized and the absolute value of the drug concentration at the tumor site should be minimized. There is a strong demand for compounds that satisfy such requirements.
【０００６】[0006]
【課題を解決するための手段】本発明者らは、このよう
な腫瘍集積性の高い、安定で且つ安全な化合物を開発す
るために鋭意研究を重ねた結果、有効且つ選択的に腫瘍
細胞膜に取り込まれるリン脂質化合物と、選択性には乏
しいが腫瘍集積性を有するホウ素化合物（カゴ型ホウ素
化合物等）を共有的に結合させることにより得られる化
合物は、腫瘍への集積性及び選択性が共に優れているこ
とを見い出した。[Means for Solving the Problems] The inventors of the present invention have conducted extensive studies to develop such a stable and safe compound having high tumor accumulating property, and as a result, effective and selective formation of a tumor cell membrane. A compound obtained by covalently binding a phospholipid compound to be taken in and a boron compound having poor selectivity but having tumor-accumulating property (eg, cage-type boron compound) has both tumor-accumulating property and selectivity. I found it to be excellent.
【０００７】また、当該化合物に放射性アイソトープで
あるヨウ素を導入することによって腫瘍を明確にイメー
ジングできることを見いだし、本化合物が有効な中性子
捕捉治療のホウ素キャリアのみならず治療には必須の病
巣の検出およびＢＮＣＴにおける10Ｂの病巣への集積を
推定できる手段となりうることを見い出し、本発明を完
成させるに至った。Further, it was found that tumor can be clearly imaged by introducing iodine, which is a radioactive isotope, into the compound, and that this compound can detect not only the boron carrier for the effective neutron capture therapy but also the detection of the lesion essential for the therapy. The inventors have found that it can be a means of estimating the accumulation of 10 B in a BNCT lesion, and completed the present invention.
【０００８】すなわち本発明の目的は、一般式（１）That is, the object of the present invention is to provide a compound represented by the general formula (1)
【化３】 ［式中、Ｒ1およびＲ2は[Chemical 3] [Wherein R 1 and R 2 are
【化４】 （ここで、ｎは０〜２０の数を、Ｗは放射性ヨウ素で置
換されたフェニル基、基−ＣＨ＝ＣＨＩまたは水素原子
を示す）を示し、Ｒ3はホウ素化合物から導かれた基を
示す］で表されるホウ素含有リン脂質化合物を提供する
ことである。また、本発明の別の目的は、上記ホウ素含
有リン脂質化合物（１）を有効成分とする癌の画像診断
剤および中性子捕捉療法剤を提供することである。[Chemical 4] (Wherein n represents a number of 0 to 20, W represents a phenyl group substituted with radioactive iodine, a group —CH═CHI or a hydrogen atom), and R 3 represents a group derived from a boron compound. ] It is providing the boron containing phospholipid compound represented by these. Another object of the present invention is to provide an image diagnostic agent for cancer and a neutron capture therapeutic agent containing the boron-containing phospholipid compound (1) as an active ingredient.
【０００９】本発明のホウ素含有リン脂質化合物（１）
は、下式に従い放射性ヨード標識リン脂質化合物（２）
と、いわゆる10Ｂキャリアと言われるホウ素化合物
（３）を結合させることによって得られる。Boron-containing phospholipid compound of the present invention (1)
Is a radioactive iodine-labeled phospholipid compound (2) according to the following formula:
And a boron compound (3) which is a so-called 10 B carrier.
【化５】 （式中、Ｒ1、Ｒ2およびＲ3は前記した意味を有する）[Chemical 5] (In the formula, R 1 , R 2 and R 3 have the above-mentioned meanings)
【００１０】上記反応における放射性ヨード標識リン脂
質化合物（１）は、末端に標識ヨウ素置換フェニル基若
しくは標識ヨウ素置換エチレン基を有するジアシルグリ
セロールまたはジアルキルグリセリルエーテルに塩化ホ
スホニル等のリン化合物を作用させることにより得られ
るリン脂質であり、具体的な化合物としては、ジアシル
グリセロ−３−ホスホリルカルボラン、ジアシルグリセ
ロ−３−ホスホリルメルカプトウンデカハイドロドデカ
ボレート等を挙げることができる。The radioiodine-labeled phospholipid compound (1) in the above reaction is prepared by reacting a phosphorus compound such as phosphonyl chloride with diacylglycerol or dialkylglyceryl ether having a labeled iodine-substituted phenyl group or a labeled iodine-substituted ethylene group at the terminal. Specific examples of the phospholipid obtained include diacylglycero-3-phosphorylcarborane, diacylglycero-3-phosphorylmercaptoundecahydrododecarbarate, and the like.
【００１１】また、ジアシルグリセロールおよびジアル
キルグリセリルエーテルの末端のヨウ素標識は常法にし
たがって行うことができ、標識に用いる放射性ヨウ素と
しては131Ｉ、125Ｉ、123Ｉ等が利用される。Further, the iodine labeling of the terminals of diacylglycerol and dialkylglyceryl ether can be carried out by a conventional method, and 131 I, 125 I, 123 I etc. are used as radioactive iodine used for labeling.
【００１２】一方のホウ素化合物（３）としては、腫瘍
への取り込みが高く、かつ多くのホウ素原子を含む化合
物として知られている、メルカプトウンデカヒドロドデ
カボレート（ＢＳＨ）、カルボラン等のカゴ型ホウ素化
合物を利用することができる。 なお、前記式中で基Ｒ3
はホウ素化合物から末端の水素原子を取り去った基を意
味する。On the other hand, as the boron compound (3), cage-type boron such as mercaptoundecahydrododecaborate (BSH) and carborane, which are known as compounds having high uptake into tumor and containing many boron atoms. Compounds can be utilized. In the above formula, the group R 3
Means a group obtained by removing a terminal hydrogen atom from a boron compound.
【００１３】放射性ヨード標識リン脂質化合物（２）と
ホウ素化合物（３）との反応は、通常のリン酸エステル
化反応、例えばチオニルクロライドによるクロル化のあ
と縮合反応を行うか、あるいはＤＣＣを用いる縮合反応
による方法等にしたがって行えば良い。The reaction between the radioactive iodine-labeled phospholipid compound (2) and the boron compound (3) is carried out by a conventional phosphoric esterification reaction, for example, chlorination with thionyl chloride followed by condensation reaction, or condensation using DCC. It may be carried out according to a reaction method or the like.
【００１４】上記の如くして得られる放射性ヨード標識
リン脂質化合物（１）は、癌の画像診断剤として利用す
ることができる。The radioiodine-labeled phospholipid compound (1) obtained as described above can be used as an image diagnostic agent for cancer.
【００１５】放射性ヨード標識リン脂質化合物（１）を
用いて癌の画像診断剤を調製するには、当該化合物をア
ルブミン等を含む生理食塩水に溶解した後、常法にした
がって製剤化すれば良い。この癌の画像診断剤は、癌の
部位、求める画像の鮮明度等によっても相違するが、一
般には一回１８５〜２５９ＭＢｑ程度の放射能量を投与
すれば良い。In order to prepare an image diagnostic agent for cancer using the radioiodine-labeled phospholipid compound (1), the compound may be dissolved in a physiological saline solution containing albumin and the like and then formulated according to a conventional method. . Although the diagnostic agent for cancer is different depending on the site of cancer, the sharpness of the image to be obtained, etc., in general, a dose of about 185 to 259 MBq of radioactivity may be administered once.
【００１６】また、中性子捕捉療法剤（ＢＮＣＴ）も上
記と同様調製できるが、この用途で用いる場合は、本発
明化合物（１）中のホウ素キャリア濃度（基Ｒ3のホウ
素量）、癌の大きさおよび部位、照射する中性子の強度
および時間等を勘案し、使用量を定めれば良い。A neutron capture therapeutic agent (BNCT) can also be prepared in the same manner as above, but when it is used for this purpose, the boron carrier concentration (boron amount of the group R 3 ) in the compound (1) of the present invention, the size of cancer. The amount to be used may be determined in consideration of the size and site, the intensity and time of neutrons to be irradiated.
【００１７】[0017]
【発明の効果】本発明は、腫瘍の局在を画像化して腫瘍
の診断を可能とすると共にホウ素中性子捕捉療法（ＢＮ
ＣＴ）においては腫瘍へのホウ素の取り込み量の算出が
容易且つ客観的に行うことができ、同時にＢＮＣＴにお
いてその治療効果を飛躍的に増大させる化合物を提供す
るものである。INDUSTRIAL APPLICABILITY The present invention makes it possible to diagnose a tumor by imaging the localization of the tumor, and at the same time, boron neutron capture therapy (BN
In CT), the amount of boron uptake into the tumor can be easily and objectively calculated, and at the same time, a compound that dramatically increases the therapeutic effect in BNCT is provided.
【００１８】すなわち、放射性アイソトープで標識され
た本発明のホウ素含有リン脂質化合物（１）を用いて核
医学画像診断例えばＳＰＥＣＴを実施することにより腫
瘍の局在を確認し、併せてＢＮＣＴにおいては腫瘍組織
中の10Ｂ濃度をきわめて容易且つ正確に求めることが出
来る化合物であり、さらにはきわめて有効なＢＮＣＴ用
薬剤となる化合物を提供するものである。That is, the localization of the tumor was confirmed by carrying out nuclear medicine imaging, for example, SPECT, using the boron-containing phospholipid compound (1) of the present invention labeled with a radioactive isotope, and at the same time, in BNCT, the tumor was detected. The present invention provides a compound capable of extremely easily and accurately determining the 10 B concentration in a tissue, and further provides a compound which is an extremely effective drug for BNCT.
【００１９】[0019]
【実施例】次に実施例を挙げて本発明を更に詳しく説明
するが、本発明はこれら実施例によりなんら制約される
ものではない。The present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.
【００２０】実 施 例 １ １５−（４−［123Ｉ］ ヨードフェニル）ペンタデカン
酸（123Ｉ−ＩＰＰＡ）の合成：テフロン製攪拌子を入
れた３ｍｌのミニバイアルに、Ｎａ123Ｉ溶液 ３７０Ｍ
Ｂｑを加え、窒素ガスを吹き込みながら加熱乾固した。
次にトリフルオロ酢酸タリウム（東京化成） １ｍｇを
含むトリフルオロ酢酸 ２５０μｌに、１５−フェニル
ペンタデカン酸 １ｍｇを溶解した液を加え、１０５℃
にて約１０分間加熱した。Example 1 Synthesis of 15- (4- [ 123 I] iodophenyl) pentadecanoic acid ( 123 I-IPPA): Na 123 I solution 370M was added to a 3 ml mini vial containing a Teflon stir bar.
Bq was added, and the mixture was heated to dryness while blowing nitrogen gas.
Next, a solution of 1 mg of 15-phenylpentadecanoic acid dissolved in 250 μl of trifluoroacetic acid containing 1 mg of thallium trifluoroacetate (Tokyo Kasei) was added, and the mixture was heated to 105 ° C.
It was heated at about 10 minutes.
【００２１】ミニバイアル中に窒素ガスを吹き付けて溶
媒を留去し、テトラヒドロフラン２００μｌを加えて残
渣を溶解した後、高速液体クロマトグラフィー［ウォー
ターズ社製、カラム：マイクロボンダスフェア１５μ
１００Ａ ７.８×３００ｍｍ、溶媒：テトラヒドロフラ
ン／アセトニトリル／水 ６０／２０／２０、流速：２
ｍｌ／ｍｉｎ］により精製を行い、123Ｉ−ＩＰＰＡを
得た。精製された123Ｉ−ＩＰＰＡはＨＰＬＣ分析によ
って高純度であることが確認された。 その保持時間は
およそ１０.５分であった。（図１）Nitrogen gas was blown into the mini vial to remove the solvent, and 200 μl of tetrahydrofuran was added to dissolve the residue. Then, high performance liquid chromatography [Waters, column: Microbonder sphere 15 μm] was used.
100A 7.8 × 300 mm, solvent: tetrahydrofuran / acetonitrile / water 60/20/20, flow rate: 2
ml / min] to obtain 123 I-IPPA. The purified 123 I-IPPA was confirmed to be highly pure by HPLC analysis. The retention time was approximately 10.5 minutes. (Fig. 1)
【００２２】実 施 例 ２ １−（１５−（４−［123Ｉ］ ヨードフェニル）ペンタ
デカノイル−２−ステアロイルーグリセロール（ラセミ
体）（123Ｉ−１,２−ｒａｃ−ＤＡＧ）の合成123 Ｉ−ＩＰＰＡ ２００ＭＢｑを濃縮乾固し、２５ｍｌ
のなす型フラスコに無水ジクロロメタン １ｍｌ及び塩
化チオニル １００μｌと共に取り、３０分間攪拌し、
１５−（４−［125Ｉ］ ヨードフェニル）ペンタデカン
酸のクロリド溶液とした。 溶媒のジクロロメタン及び
未反応の塩化チオニルを加熱下完全に留去した後、これ
に２−モノステアリン ２ｍｇ及び４−ジメチルアミノ
ピリジン ２ｍｇを含む無水ジクロロメタン溶液 １ｍｌ
を加え、３０分間攪拌した。[0022] Synthesis of implementation Example 2 1- (15- (4- [123 I] iodophenyl) pentadecanoyl-2-stearoyl Lou glycerol (racemate) (123 I-1,2-rac -DAG) 123 25 ml of I-IPPA 200MBq was concentrated to dryness.
Take in an eggplant-shaped flask with 1 ml of anhydrous dichloromethane and 100 μl of thionyl chloride and stir for 30 minutes.
A chloride solution of 15- (4- [ 125 I] iodophenyl) pentadecanoic acid was prepared. After completely distilling off the solvent dichloromethane and unreacted thionyl chloride under heating, 1 ml of an anhydrous dichloromethane solution containing 2 mg of 2-monostearin and 2 mg of 4-dimethylaminopyridine.
Was added and stirred for 30 minutes.
【００２３】溶媒留去後、残渣をヘキサンで溶解し、Ｈ
ＰＬＣ［ウォーターズ社製、カラム：ゾルバックスＳＩ
Ｌカラム ４.９×２４０ｍｍ ＤｕＰｏｎｔ社製、溶
媒：ヘキサン／イソプロピルアルコール ９８／２、流
速：２ｍｌ／ｍｉｎ］により精製し、123Ｉ−１,２−ｒ
ａｃ−ＤＡＧを得た。123 Ｉ−１,２−ｒａｃ−ＤＡＧは、１−（１５−（４−
［123Ｉ］ ヨードフェニル）ペンタデカノイル−３−ス
テアロイルーグリセロール（ラセミ体）（123Ｉ−１,３
−ｒａｃ−ＤＡＧ）溶出後に検出され、その保持時間は
約６分であった。（図２） 精製123Ｉ−１,２−ｒａｃ−ＤＡＧのＨＰＬＣクロマト
グラムを図３に示す。After distilling off the solvent, the residue is dissolved in hexane, and H 2
PLC [Waters, column: Zorbax SI
L column 4.9 × 240 mm, manufactured by DuPont, solvent: hexane / isopropyl alcohol 98/2, flow rate: 2 ml / min], and purified by 123 I-1,2-r.
Ac-DAG was obtained. 123 I-1,2-rac-DAG is 1- (15- (4-
[ 123 I] Iodophenyl) pentadecanoyl-3-stearoyl-glycerol (racemic) ( 123 I-1,3
-Rac-DAG) was detected after elution and its retention time was about 6 minutes. (FIG. 2) The HPLC chromatogram of the purified 123 I-1,2-rac-DAG is shown in FIG.
【００２４】実 施 例 ３ １−（１５−４−［123Ｉ］ ヨードフェニル）ペンタデ
カノイル−２−ステアロイルーグリセロ−３−ホスホリ
ルメルカブトウンデカヒドロデカート（123Ｉ−１,２−
ｒａｃ−ＰＡ−ＢＳＨ）の合成：123Ｉ−１,２−ｒａｃ
−ＤＡＧ ７４ＭＢｑを含む１０ｍｌなす型フラスコ
に、ジクロロメタン ５００μｌを加えて溶解し、塩化
ホスホニル ５μｌを加えて３０分間攪拌した後、蒸発
乾固する。 ジクロロメタンで再溶解した後、メルカプ
トウンデカヒドロドデカボレート（ＢＳＨ） １０ｍｇ
を加えてさらに３０分間攪拌した。The implementation Example 3 1- (15-4- [123 I] iodophenyl) pentadecanoyl-2-stearoyl Lou glycerophosphate 3- phosphoryl Mel helmet down decahydro de basket (123 I-1,2-
rac-PA-BSH): 123 I-1,2-rac
-To a 10 ml eggplant-shaped flask containing DAG 74MBq, 500 μl of dichloromethane was added to dissolve it, 5 μl of phosphonyl chloride was added, and the mixture was stirred for 30 minutes, and then evaporated to dryness. After redissolving in dichloromethane, 10 mg of mercaptoundecahydrododecaborate (BSH)
Was added and stirred for another 30 minutes.
【００２５】溶媒留去後、ヘキサン １ｍｌを加えて洗
浄し、残渣についてシリカゲル薄層クロマトグラフィー
分取（展開溶媒：クロロホルム／メタノール／アンモニ
ア／水＝２０／１５／３／２）を行い、最終目的物を得
た。 シリカゲル薄層クロマトグラムを図４に示す。After distilling off the solvent, 1 ml of hexane was added for washing, and the residue was subjected to silica gel thin-layer chromatography fractionation (developing solvent: chloroform / methanol / ammonia / water = 20/15/3/2) for the final purpose. I got a thing. The silica gel thin layer chromatogram is shown in FIG.
【００２６】試 験 例 １123 Ｉ−１,２−ｒａｃ−ＰＡ−ＢＳＨの担癌ラット体内
分布：培養Ｃ６グリオーマ細胞を遠沈後、ラットの下肢
に注射して固形腫瘍を形成させる。１週間後固形腫瘍よ
り細胞細片を切り出し、これをラット脳皮質下に移植
し、担癌ラットを作成した。 Ｃ６グリオーマ固形腫瘍
を移植してから２０日後、移植ラットに尾静脈より123
Ｉ−１,２−ｒａｃ−ＰＡ−ＢＳＨ １８５０ＫＢｑを投
与し、３時間後にラットの脳腫瘍部分、小脳、肺、肝
臓、腎臓及び血液を採取し、重量測定とシングルチャン
ネルガンマカウンターによる放射能測定を行い、投与放
射能に対する組織１ｇ当たりの取り込み率（％ＩＤ／
ｇ）を算出した。この結果を表１に示す。Test Example 1 123 I-1,2-rac-PA-BSH distribution in tumor-bearing rats: After incubating cultured C6 glioma cells, they were injected into the lower limbs of the rats to form solid tumors. One week later, cell debris was cut out from the solid tumor and transplanted under the rat brain cortex to prepare a tumor-bearing rat. 20 days after the transplantation of C6 glioma solid tumor, 123
I-1,2-rac-PA-BSH 1850KBq was administered, and after 3 hours, rat brain tumor part, cerebellum, lung, liver, kidney and blood were collected, and weight measurement and radioactivity measurement by single channel gamma counter were performed. , Uptake rate per 1 g of tissue relative to administered radioactivity (% ID /
g) was calculated. Table 1 shows the results.
【００２７】 [0027]
【００２８】試 験 例 ２ 上記試験例１と同様にして作成したＣ６グリオーマ固形
腫瘍の担癌ラットに12 3Ｉ−１,２−ｒａｃ−ＰＡ−ＢＳ
Ｈ １８５０ＫＢｑを尾静脈より投与し、３時間後に大
脳を摘出、ドライアイスにより凍結させ、ミクロトーム
（中川製作所社製）にて２０μｍ厚の組織断片を作成し
た。イメージングプレートに組織切片を密着させて封入
した後、画像解析装置（富士フィルム社製）を用いて３
９時間の露光を行い、脳オートラジオグラムを得た（参
考写真参照）。Test Example 2 C6 glioma solid prepared in the same manner as in Test Example 1 above
In tumor-bearing rats12 3I-1,2-rac-PA-BS
H 1850 KBq was administered via the tail vein, and 3 hours later,
The brain is removed, frozen with dry ice, and microtome
Create a 20 μm thick tissue fragment (made by Nakagawa Seisakusho).
It was Enclose the tissue section in close contact with the imaging plate
After that, using an image analysis device (Fuji Film Co., Ltd.), 3
After exposure for 9 hours, a brain autoradiogram was obtained (see
See the photo).
【図１】 123Ｉ−ＩＰＰＡのＨＰＬＣ分析結果を示す
図面。FIG. 1 is a drawing showing HPLC analysis results of 123 I-IPPA.
【図２】 123Ｉ−１,２−ｒａｃ−ＤＡＧのＨＰＬＣ分
析結果を示す図面。FIG. 2 is a drawing showing HPLC analysis results of 123 I-1,2-rac-DAG.
【図３】 精製123Ｉ−１,２−ｒａｃ−ＤＡＧのＨＰＬ
Ｃクロマトグラムを示す図面。FIG. 3 HPL of purified 123 I-1,2-rac-DAG
Drawing which shows C chromatogram.
【図４】 123Ｉ−１,２−ｒａｃ−ＰＡ−ＢＳＨのシリ
カゲル薄層クロマトグラムを示す図面。 図面中、Ａは123Ｉ−１,２−ｒａｃ−ＰＡ、Ｂは123Ｉ
−１,２−ｒａｃ−ＤＡＧ、Ｃは反応液、Ｄは、123Ｉ−
１,２−ｒａｃ−ＰＡ−ＢＳＨ（目的物）を示す。 以 上FIG. 4 is a drawing showing a silica gel thin-layer chromatogram of 123 I-1,2-rac-PA-BSH. In the drawing, A is 123 I-1,2-rac-PA and B is 123 I.
-1,2-rac-DAG, C is the reaction solution, D is 123 I-
1,2-rac-PA-BSH (target product) is shown. that's all
───────────────────────────────────────────────────── フロントページの続き (71)出願人 594148232 藤井 亮 京都府京都市伏見区竹田中川原町57番地の 24 (71)出願人 594148243 上田 聖 京都府京都市左京区岩倉忠在地町11番地の 18 (72)発明者 今堀 良夫 京都府京都市上京区今出川通り掘川東入飛 鳥井町252番地 フォルム掘川今出川506号 (72)発明者 脇田 員男 京都府京都市伏見区深草西浦町１丁目10番 地の３ロイヤル深草 407号 (72)発明者 藤井 亮 京都府京都市伏見区竹田中川原町57番地の 24 (72)発明者 上田 聖 京都府京都市左京区岩倉忠在地町11番地の 18 (72)発明者 井上 実 千葉県山武郡成東町津辺150−１ シティ ハイム今関Ａ棟202号室 (72)発明者 田沢 周作 千葉県印旛郡富里町七栄52−22 ─────────────────────────────────────────────────── ─── Continuation of the front page (71) Applicant 594148232 Ryo Fujii 24, 57 Takeda Nakagawara-cho, Fushimi-ku, Kyoto-shi, Kyoto 24 (71) Applicant 594148243 Ueda St. 11 Iwakura Tadashichi-cho, Sakyo-ku, Kyoto-shi, Kyoto 18 (72) Inventor Yoshio Imabori, Nozomi Higashiiri, 252 Irikawa-dori, Imadegawa-dori, Kamigyo-ku, Kyoto, Japan Form No. 506, Imadegawa, Horikawa Formosa (72) Inoue, Takuo Wakita 1-10, Fukakusa Nishiura-cho, Fushimi-ku, Kyoto-shi, Kyoto Address 3 Royal Fukakusa No. 407 (72) Inventor Ryo Fujii 24 at 57, Takeda Nakagawara-cho, Fushimi-ku, Kyoto-shi, Kyoto Prefecture (72) Inventor Kiyoshi Ueda 18 at 11-Iwakura-Tadachi-machi, Sakyo-ku, Kyoto-shi, Kyoto Prefecture (72) Inventor Minoru Inoue 150-1 Tsunabe, Narito-cho, Sanmu-gun, Chiba City Heim Imazeki Room A Room 202 (72) Inventor Shusaku Tazawa 52-22 Nanae, Tomisato-cho, Inba-gun, Chiba Prefecture
Claims (8)
換されたフェニル基、基−ＣＨ＝ＣＨＩまたは水素原子
を示す）を示し、Ｒ3はホウ素化合物から導かれた基を
示す］で表されるホウ素含有リン脂質化合物。1. A compound represented by the general formula (1): [Wherein R 1 and R 2 are as follows: (Wherein n represents a number of 0 to 20, W represents a phenyl group substituted with radioactive iodine, a group —CH═CHI or a hydrogen atom), and R 3 represents a group derived from a boron compound. ] The boron containing phospholipid compound represented by these.
Ｉから選ばれたものである請求項第１項記載のホウ素含
有リン脂質化合物。2. The radioactive iodine is 131 I, 125 I or 123.
The boron-containing phospholipid compound according to claim 1, which is selected from I.
合物がカゴ型ホウ素化合物から導かれる基である請求項
第１項または第２項記載のホウ素含有リン脂質化合物。3. The boron-containing phospholipid compound according to claim 1, wherein the boron compound represented by R 3 in the general formula (1) is a group derived from a cage-type boron compound.
ロドデカボレートから導かれたものである請求項第１項
ないし第３項記載の何れかの項記載のホウ素含有リン脂
質化合物。4. The boron-containing phospholipid compound according to any one of claims 1 to 3, wherein the boron compound is derived from mercaptoundecahydrododecaborate.
かれたものである請求項第１項ないし第３項記載の何れ
かの項記載のホウ素含有リン脂質化合物。5. The boron-containing phospholipid compound according to any one of claims 1 to 3, wherein the boron compound is derived from a carborane derivative.
第５項記載のホウ素含有リン脂質化合物。6. The boron-containing phospholipid compound according to claim 5, wherein the boron compound is carborane.
に記載のホウ素含有リン脂質化合物を有効成分とする癌
の画像診断剤。7. An image diagnostic agent for cancer, which comprises the boron-containing phospholipid compound according to any one of claims 1 to 6 as an active ingredient.
に記載のホウ素含有リン脂質化合物を有効成分とする中
性子捕捉療法剤。8. A neutron capture therapeutic agent containing the boron-containing phospholipid compound according to any one of claims 1 to 6 as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6209325A JPH0853475A (en) | 1994-08-11 | 1994-08-11 | Phospholipid compound containing radioactive iodine-labeled boron |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6209325A JPH0853475A (en) | 1994-08-11 | 1994-08-11 | Phospholipid compound containing radioactive iodine-labeled boron |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0853475A true JPH0853475A (en) | 1996-02-27 |
Family
ID=16571081
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6209325A Withdrawn JPH0853475A (en) | 1994-08-11 | 1994-08-11 | Phospholipid compound containing radioactive iodine-labeled boron |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0853475A (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0754690A1 (en) * | 1995-07-21 | 1997-01-22 | President of TOHOKU UNIVERSITY | Gadolinium-DTPA complex containing carborane unit, intermediates thereof and method of synthesizing them |
| US6248553B1 (en) | 1998-10-22 | 2001-06-19 | Atairgin Technologies, Inc. | Enzyme method for detecting lysophospholipids and phospholipids and for detecting and correlating conditions associated with altered levels of lysophospholipids |
| US6500633B1 (en) | 2000-04-26 | 2002-12-31 | Atairgin Technologies, Inc. | Method of detecting carcinomas |
| JP2008013498A (en) * | 2006-07-06 | 2008-01-24 | Stella Chemifa Corp | Boron-containing compound and liposome using the same |
| JP2008074817A (en) * | 2006-09-25 | 2008-04-03 | Hiroyuki Nakamura | Boron ion cluster type cholesterol and liposome |
| JP2008094730A (en) * | 2006-10-06 | 2008-04-24 | Hiroyuki Nakamura | Boron-containing compound and liposome using the same |
| JP2017101930A (en) * | 2015-11-30 | 2017-06-08 | 学校法人 新潟科学技術学園 | Diagnosis device, treatment device, and drugs |
| JP2019156796A (en) * | 2018-03-15 | 2019-09-19 | 国立大学法人大阪大学 | Method for labeling radioisotope to boron cluster lipid and method for introducing labeled boron cluster lipid into virus particle |
| WO2023088134A1 (en) * | 2021-11-22 | 2023-05-25 | 北京大学 | Novel boronsome facilitating diagnosis and treatment |
-
1994
- 1994-08-11 JP JP6209325A patent/JPH0853475A/en not_active Withdrawn
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0754690A1 (en) * | 1995-07-21 | 1997-01-22 | President of TOHOKU UNIVERSITY | Gadolinium-DTPA complex containing carborane unit, intermediates thereof and method of synthesizing them |
| US6248553B1 (en) | 1998-10-22 | 2001-06-19 | Atairgin Technologies, Inc. | Enzyme method for detecting lysophospholipids and phospholipids and for detecting and correlating conditions associated with altered levels of lysophospholipids |
| US6255063B1 (en) | 1998-10-22 | 2001-07-03 | Atairgin Technologies, Inc. | Disease conditions by measuring lysophosphatidic acid |
| US6500633B1 (en) | 2000-04-26 | 2002-12-31 | Atairgin Technologies, Inc. | Method of detecting carcinomas |
| JP2008013498A (en) * | 2006-07-06 | 2008-01-24 | Stella Chemifa Corp | Boron-containing compound and liposome using the same |
| JP2008074817A (en) * | 2006-09-25 | 2008-04-03 | Hiroyuki Nakamura | Boron ion cluster type cholesterol and liposome |
| JP2008094730A (en) * | 2006-10-06 | 2008-04-24 | Hiroyuki Nakamura | Boron-containing compound and liposome using the same |
| JP2017101930A (en) * | 2015-11-30 | 2017-06-08 | 学校法人 新潟科学技術学園 | Diagnosis device, treatment device, and drugs |
| JP2019156796A (en) * | 2018-03-15 | 2019-09-19 | 国立大学法人大阪大学 | Method for labeling radioisotope to boron cluster lipid and method for introducing labeled boron cluster lipid into virus particle |
| WO2023088134A1 (en) * | 2021-11-22 | 2023-05-25 | 北京大学 | Novel boronsome facilitating diagnosis and treatment |
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