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.

采用低剂量替莫唑胺传代法，建立了恶性胶质瘤耐替莫唑胺亚系。我们分析了单药治疗（TMZ，贝伐单抗（BV））和联合治疗（TMZ/干扰素-β (IFN), TMZ/BV, TMZ/IFN/BV）的疗效，基于抗facbc和mehionine （Met）摄取和肿瘤增殖。虽然TMZ和IFN联合治疗显著降低了TMZ耐药细胞的抗facbc和Met摄取和增殖，但在体外没有发现BV的额外作用。在接种的脑肿瘤中，TMZ和IFN联合治疗显著降低了TMZ耐药肿瘤的示踪剂积累和增殖，其程度与未用药肿瘤相当，而与BV联合治疗时，两种肿瘤的示踪剂积累和增殖均进一步降低。与Met一样，Anti-FACBC对IFN和BV联合治疗TMZ的早期肿瘤反应比MRI更敏感，而MRI不适用于BV联合抗血管生成治疗后的肿瘤描绘和治疗反应评估。