Synthesis and evaluation of BPA-Gd-DTPA complex as an MRI contrast agent and as a carrier for neutron capture therapy

MRI造影剤及び中性子捕捉療法用キャリアとしてのBPA-Gd-DTPA化合物の合成法と評価

高橋 和範*; 中村 浩之*; 古本 祥三*; 山本 和喜 ; 松村 明*; 福田 寛*; 山本 嘉則*

Takahashi, Kazunori*; Nakamura, Hiroyuki*; Furumoto, Shozo*; Yamamoto, Kazuyoshi; Matsumura, Akira*; Fukuda, Hiroshi*; Yamamoto, Yoshinori*

中性子捕捉療法用キャリアーとしてMRI造影剤に使用されているGd-DTPAにBPAを付加したBPA-Gd-DTPA化合物を合成した。ラットのAH109A hepatoma腫瘍へ本化合物を注入し生体内薬剤分布の研究を実行した。Gdとホウ素の集積率は即発線分析法によって測定した。腫瘍集積率(%ID/g)は、注入後、20分及び6分にそれぞれ1%及び0.3%で、以前に報告したcarborane-Gd-DTPAより高かった。しかし、肝臓及び腎臓の集積率も非常に高く、腫瘍/血液比はBPA自体(ca.3.0)と比較して、0.38と非常に低かった。ラットの線オートラジオグラフィでは、周囲の筋肉と比較して腫瘍のホウ素濃度はより高い値を示した。本化合物の腫瘍選択性はcarborane-Gd-DTPAより高かったが、良い化合物の合成法の研究を継続して行う。

We synthesized a BPA-Gd-DTPA compound, as a carrier for neutron capture therapy to be used for MRI contrast media. Pinanediol was used as the protective group for B(OH)2 group of BPA, and the BPA unit was connected to the DTPA framework through an amide bond. The biodistribution studies were performed after injection of the compound into AH109A hepatoma bearing Donryu rats. The concentrations of Gd and boron were measured by prompt g-ray analyses. The tumor uptakes (% ID/g) were 1% and 0.3% at 20 min and 60 min after injection, respectively and were higher than that of carborane-Gd-DTPA, which we previously reported. However, liver and kidney uptake was very high and tumor/blood ratio was very low (0.38) compared to that of BPA itself (ca. 3.0). Alfa autoradiogram of a tumor bearing rat showed higher concentration of boron in the tumor compared to surrounding muscle and very high in the intestine. Although tumor selectivity of the compound was higher than that of carborane-Gd-DTPA, further studies of the synthesis and in vivo evaluation of better binary compounds are continuing.