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

用低剂量替莫唑胺（TMZ）传代建立胶质母细胞瘤耐药亚系。我们基于抗FACBC和甲硫氨酸（Met）摄取和肿瘤增殖分析了单药（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。尽管TMZ和IFN联合治疗显著降低了TMZ耐药细胞的抗FACBC和Met摄取以及增殖，但在体外未观察到BV的额外作用。在接种的脑肿瘤中，TMZ和IFN的组合治疗显著降低了TMZ耐药肿瘤的示踪剂积累和增殖，与药物初始肿瘤一样多，并且在与BV的组合中，这两种肿瘤的示踪剂积累和增殖甚至进一步降低。与Met一样，抗FACBC对TMZ联合IFN和BV治疗的早期肿瘤反应比MRI更敏感，而MRI不适用于肿瘤描绘和BV抗血管生成治疗后的治疗反应评估。

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.