Experimental studies of synthesized amino acid analog anti-FACBC as imaging biomarker to monitor treatment response of glioblatomas to temozolomide therapy with interferon-. and bevacizumab

合成氨基酸类似物抗 FACBC 作为成像生物标志物监测胶质母细胞瘤对干扰素替莫唑胺治疗反应的实验研究。

• 批准号: 22591602
• 负责人: SASAJIMA Toshio
• 金额: $ 2.75万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591602/
• 关键词: 悪性脳腫瘍; 腫瘍イメージング; 人工アミノ酸トレーサ; テモゾロミド; 増殖能; インターフェロンβ; ベバシズマブ; 人工アミノ酸; インターフェロン; 抗血管新生療法; メチオニン; 腫瘍増殖能

The temozolomide (TMZ)-resistant subline of glioblastoma was established by subculture with low-dose TMZ. We analyzed the efficacy of treatment with single-agent (TMZ, bevacizumab (BV)) and combination therapy (TMZ/interferon-β (IFN), TMZ/BV, TMZ/IFN/BV) based on both anti-FACBC and mehionine (Met) uptake and tumor proliferation. Although treatment with a combination of TMZ and IFN significantly decreased both anti-FACBC and Met uptake and proliferation of TMZ-resistant cells as much as drug-naive cells, no additional effect of BV was noted in vitro. In the inoculated brain tumors, treatment with a combination of TMZ and IFN significantly decreased the tracer accumulation and proliferation of TMZ-resistant tumor as much as drug-naive tumor, and in a combination with BV, those of both tumors decreased even further. Anti-FACBC, like Met, was more sensitive than MRI for early tumor response to TMZ therapy with IFN and BV, whereas MRI was unsuitable for tumor delineation and assessment of treatment response after the antiangiogenic therapy using BV.

我们通过低剂量TMZ传代培养建立了替莫唑胺（TMZ）耐药的胶质母细胞瘤亚系，我们分析了单药（TMZ、贝伐单抗（BV））和联合治疗（TMZ/干扰素-β（IFN））的疗效。 、TMZ/BV、TMZ/IFN/BV）基于抗 FACBC 和蛋氨酸 (Met) 摄取和肿瘤增殖。 TMZ 和 IFN 显着降低抗 FACBC 和 Met 的摄取以及 TMZ 抗性细胞的增殖，与未接受药物的细胞一样，在体外接种的脑肿瘤中未发现 BV 的额外作用。 IFN 显着降低了 TMZ 耐药肿瘤的示踪剂积累和增殖，与未接受药物治疗的肿瘤一样，与 BV 联合使用时，两种肿瘤的示踪剂积累和增殖都进一步降低，与 Met 一样，比 Met 更敏感。 MRI 适用于 TMZ 治疗（IFN 和 BV）的早期肿瘤反应，而 MRI 不适用于肿瘤描绘和评估 BV 抗血管生成治疗后的治疗反应。