Purpose

The present study analyzed different protocols of administration of boronophenylalanine (BPA) and sodium butyrate (NaB) to increase the BNCT efficacy for poorly differentiated thyroid cancer (PDTC).

Materials and methods

Nude mice implanted with human PDTC cells (WRO) were distributed into four protocols: 1) BPA; 2) BPA + ip NaB; 3) BPA + oral NaB; 4) Control. Biodistribution and histologic studies were performed. LAT (BPA transporter) isoforms gene expression was assessed by RT-PCR.

Results

Tumor growth delay was observed in animals of the Protocol #3 (p < 0.05). NaB (Protocol #2) increased tumor boron uptake 2-h post BPA injection (p < 0.05). On the other hand, NaB upregulated the expression of all the isoforms of the LAT transporter in vitro. Histologic studies showed a significant decrease of mitotic activity and an increase of vacuoles in tumors of Protocol #3. Neutrons alone or combined with NaB caused some tumor growth delay (p < 0.05), while in the BNCT and BNCT + NaB groups, there was a halt in tumor growth in 70 and 80% of the animals, respectively.

Conclusions

Intraperitoneally administration of NaB increased boron uptake while oral administration for a longer period of time induced tumor growth delay previous to BPA administration. The use of NaB via ip would optimize the irradiation results.

中文翻译：

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使用组蛋白去乙酰化酶抑制剂 (HDACI) 丁酸钠作为辅助药物治疗低分化甲状腺癌 (PDTC) 的硼中子俘获疗法 (BNCT) 的实验研究。

目的

本研究分析了硼苯丙氨酸 (BPA) 和丁酸钠 (NaB) 的不同给药方案，以提高 BNCT 对低分化甲状腺癌 (PDTC) 的疗效。

材料和方法

植入人类 PDTC 细胞 (WRO) 的裸鼠分为四种方案：1) BPA；2) BPA + ip NaB；3) BPA+口服NaB；4) 控制。进行了生物分布和组织学研究。LAT（BPA 转运蛋白）同种型基因表达通过 RT-PCR 进行评估。

结果

在方案#3 的动物中观察到肿瘤生长延迟（p < 0.05）。NaB（方案#2）在 BPA 注射后 2 小时增加了肿瘤硼的摄取（p < 0.05）。另一方面，NaB 上调了体外LAT 转运蛋白所有同种型的表达。组织学研究表明，方案#3 的肿瘤中有丝分裂活性显着降低，空泡增加。中子单独或与 NaB 组合导致一些肿瘤生长延迟（p < 0.05），而在 BNCT 和 BNCT + NaB 组中，分别有 70% 和 80% 的动物肿瘤生长停止。

结论

NaB 的腹膜内给药增加了硼的摄取，而在 BPA 给药之前较长时间的口服给药诱导了肿瘤生长延迟。通过 ip 使用 NaB 将优化辐照结果。