Sakata I, Takata H, Ikeuchi M, Hirata N, Inui H, Nakajima S, Yamauchi H, Koshimizu K
Toyo Hakka Kogyo Co., Ltd., Okayama, Japan.
Yakugaku Zasshi. 1990 Dec;110(12):916-21. doi: 10.1248/yakushi1947.110.12_916.
A carrier for a new tumor imaging agent, a bifunctional chelating agent (BCA)-coupled porphyrin (ATN-2), has been synthesized from protoporphyrin dimethyl ester in 4 steps. At first, the hydrobromination of protoporphyrin dimethyl ester is carried out to obtain a monobromo derivative. The derivative is treated with ethylene glycol. The resulting porphyrin has an ether group at the either 7- or 12-position of the ring. Metallation with GaCl3 of the porphyrin having a ethylene glycol residue affords Ga-metalloporphyrin. Final condensation of the metalloporphyrin with diethylenetriaminepentaacetic acid (DT-PA) gave BCA-coupled porphyrin (ATN-2). The chelation of ATN-2 with 111InCl3 easily afforded [111In]ATN-2. This agent was used for imaging transplantable pancreatic carcinoma in Syrian golden hamster at 72 h after postinjection. The efficacy of the new agent was compared with that of [67Ga]citrate. The images with [111In]ATN-2 were found to be clearer than those with [67Ga]citrate. Therefore, ATN-2, a carrier for 111InCl3, seems to be more useful for tumor imaging agents.
一种新型肿瘤显像剂的载体，即双功能螯合剂（BCA）偶联卟啉（ATN-2），已由原卟啉二甲酯分4步合成。首先，对原卟啉二甲酯进行氢溴化反应以获得单溴衍生物。该衍生物用乙二醇处理。所得卟啉在环的7位或12位具有一个醚基。用氯化镓对具有乙二醇残基的卟啉进行金属化反应得到镓金属卟啉。金属卟啉与二乙烯三胺五乙酸（DT-PA）进行最终缩合得到BCA偶联卟啉（ATN-2）。ATN-2与氯化铟（111InCl3）螯合很容易得到[111In]ATN-2。该试剂用于在注射后72小时对叙利亚金黄地鼠的可移植胰腺癌进行显像。将该新型试剂的效能与枸橼酸镓（67Ga）的效能进行比较。发现[111In]ATN-2的图像比[67Ga]枸橼酸的图像更清晰。因此，作为氯化铟（111InCl3）载体的ATN-2似乎对肿瘤显像剂更有用。
