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

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591602
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Akita University
• Principal Investigator: SASAJIMA Toshio 秋田大学, 大学院・医学系研究科, 准教授 (40235289)
• Project Period (FY): 2010 – 2012
• Keywords: 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

Research Abstract

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.