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ホウ素熱中性子捕捉療法の適応拡大に関する研究副題:単クロ-ン抗体利用の ^<10>B集積,即発γ線による癌診断,L体単離による ^<10>BーBPAの薬効増強

扩大硼热中子俘获疗法适应症的研究副标题：利用单克隆抗体^<10>B积累、通过即时伽马射线诊断癌症、通过分离L体增强^<10>B-BPA的药效

基本信息

批准号：
02151038
负责人：
三島豊
金额：
$ 9.41万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Cancer Research
财政年份：
1990
资助国家：
日本
起止时间：
1990 至无数据
项目状态：
已结题

项目摘要

1.新発売の米国製M_2・ ^<10>B_<12>H_<12>(M:Na,Cs)を原料とし, ^<10>B抗体作用の ^<10>B化剤を合成したが純度・収量低く実用不可。同原料の精製法を案出,実用可能品を得た。2.人工抗原GM3リポソ-ムをキラ-T細胞(CTL)に働かせ,GM3モル濃度5〜9%で抗メラノ-マCTLを得,抗体との関係に論及。3.I^<128>標識763.74T抗体のP22黒色腫細胞への顕著な集積を確認後,ビオチン化763.74Tと ^<10>Bーアビジンの複合体をP22に作用させ,第13項記載のICPーMS法で,1細胞当り2.6×10^8個の ^<10>B原子の集積を証明。4. ^<10>Bーdextran含有液中のHeLa細胞に原子炉照射しRBEを算出。 ^<60>Cor1.0に対し熱中性子1.5〜2.0, ^<10>B(n,α)^7Li反応5.5〜6.0。5.マウス黒色腫細胞のX線感受株,抵抗株(感受性差Do値で30cGy)とヒト同細胞の両株(差96cGy)を得た。6. ^<10>B薬物をハムスタ-・兎・マウスに投与,即発γ線法で ^<10>B体内濃度の時間変化を追跡。ヒト2症例の診断に同法を応用。7.300,700,1500mg/kgの ^<10>BーBPAをラットに28日間連続経口投与し,摂食・摂水量,体重,臓器重量,血液検査による亜急性毒性試験実施中。8. ^<10>BーBPAのcyclodextrin錯体,fructose錯体を黒色腫担癌ハムスタ-に経口投与。前者は後者に比し血中BPA濃度の時間積分値と腫内BPA濃度は大,胃腸間内BPA残存量は小。9.酵素法により光学純度100%に近いL体とD体を得た。高速液体クロマト法でL体とD体の完全分離に成功,本法は純度検定に好適。10.数種の抗GD2単クロ-ン抗体のうち,IgG3サブクラスはヒト黒色腫担癌ヌ-ドマウスの腫瘍増殖を顕著に抑制した。 ^<10>B化すれば本療法用に有望。11.黒色腫9症例の皮膚障害より ^<10>B(n,α)^7Li反応のRBEを2.0〜2.5と推定。ラット投与重水の磁気共鳴画像を得て,組織血流測定。12.BPAの ^<18>F標識物[Fー18]ーFBPAはヒト患者の脳転移黒色腫に集積し,画像明瞭。黒色腫担癌ハムスタ-でL体の腫内集積はDL体の2倍以上。13.第3項の分析試料1mlはP22細胞2×10^5個を含みIcpーMSによる ^<10>B量は0.885ng。上記 ^<10>B集積数は目標値1×10^9に今一歩。

1. The newly developed M_2·<10>B_<12>H_<12>(M:Na,Cs) is a raw material for the synthesis of <10>B <10>antibodies with low purity and purity. The same raw material purification method is proposed, and the possible product is obtained. 2. The relationship between GM3 and CTL was discussed. 3. <128>After confirming the aggregation of 763.74T antibody in P22 black tumor cells, the complex of 763.74T antibody and <10>B antibody was identified as P22 interaction, and the aggregation of 2.6×10^8 B atoms in 1 cell was proved by ICP MS method in item 13<10>. 4. ^Calculation of <10>RBE of HeLa cells irradiated by atomic furnace in solution containing B-dextran. ^<60>Cor1.0 = 1.5 ~ 2.0, ^<10>B(n,α)= 5.5 ~ 6.0. 5. X-ray sensitive strains of black tumor cells, resistant strains (sensitivity difference Do = 30cGy) and resistant strains of the same cells (difference 96cGy) were obtained. 6. ^<10>B <10>substance concentration profile-·The same method was used for diagnosis of 2 cases. 7.300, 700, 1500mg/kg of <10>BPA was administered daily for 28 days, and the acute toxicity test was carried out in the following areas: "water consumption," body weight, weight of the instrument, blood test. 8. ^<10>BPA cyclodextrin,fructose, and black pigment. Compared with the former, the time integral of BPA concentration in blood, BPA concentration in tumor and BPA residue in gastrointestinal tract were higher and lower respectively. 9. The enzyme method is 100% optical purity. The high speed liquid chromatography method was successful in the complete separation of L and D. The method was suitable for purity determination. 10. Several anti-GD2 antibodies inhibit the proliferation of black tumors. B<10>. The treatment is expected. 11. Skin damage in 9 cases of black swelling ^<10>B(n,α)^7Li inverse RBE 2.0 ~ 2.5 presumptions. Magnetic resonance imaging of heavy water and tissue blood flow measurement were obtained. 12.BPA ^<18>F marker [F − 18]-FBPA is not suitable for patients with black swelling accumulation, the picture is clear. Black swelling is more than twice as large as DL swelling. 13. 1ml of analytical sample for item 3 contains 2×10^5 cells of P22 cells <10>and 0.885ng of B. Note above that the <10>aggregate number of ^ B is 1×10^9, which is now a step.