In vivo uptake and metabolism of α-[11C] methyl-L-tryptophan in human brain tumors
In vivo uptake and metabolism of α-[11C] methyl-L-tryptophan in human brain tumors
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DOI：
10.1038/sj.jcbfm.9600199
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发表时间：
2006-03-01
影响因子：
6.3
通讯作者：
Chugani, HT
中科院分区：
文献类型：
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作者：
Juhász, C;Chugani, DC;Chugani, HT
色氨酸代谢异常参与了肿瘤细胞增殖和免疫耐药的调节。α-[C-11]甲基L色氨酸(AMT)是一种用于活体测量大脑色氨酸代谢的正电子发射计算机断层扫描示踪剂。在本研究中，我们使用AMT PET和标准摄取值(SUV)测量了40例原发性脑肿瘤患者的肿瘤色氨酸摄取。使用血液输入数据对23名患者的色氨酸代谢进行了进一步的量化。计算分布体积(Vd‘)和代谢速率常数(k’(3))，并与磁共振成像(MRI)和组织学结果相关联。所有II~IV级胶质瘤和神经胶质瘤均表现为AMT SUV增加，包括所有复发/残留肿瘤。MRI上Gd强化与高Vd‘值相关，提示血脑屏障受损，而k’(3)值与增强无关。低级别星形细胞胶质瘤表现为色氨酸代谢增加，用k‘(3)表示。与正常皮质相比，少突胶质瘤的Vd‘值较高，k’(3)值较低。在星形细胞肿瘤中，低级别与高k‘(3)和低Vd’相关，而高级别肿瘤则相反。研究结果显示，在原发和残留/复发的胶质瘤和神经胶质瘤中，AMT摄取率很高。AMT摄取增加可能是由于色氨酸代谢增加和/或大量分布，这取决于肿瘤的类型和分级。低级别肿瘤的高色氨酸代谢率可能表明犬尿氨酸途径的激活，这是一种调节肿瘤细胞生长的机制。AMT PET可能是一种有用的分子成像方法，用于指导旨在通过作用于色氨酸代谢来控制肿瘤细胞增殖的治疗方法。
Abnormal metabolism of tryptophan has been implicated in modulation of tumor cell proliferation and immunoresistance. alpha-[C-11] Methyl-L-tryptophan (AMT) is a PET tracer to measure cerebral tryptophan metabolism in vivo. In the present study, we have measured tumor tryptophan uptake in 40 patients with primary brain tumors using AMT PET and standard uptake values (SUV). Tryptophan metabolism was further quantified in 23 patients using blood input data. Estimates of the volume of distribution (VD') and the metabolic rate constant (k'(3)) were calculated and related to magnetic resonance imaging (MRI) and histology findings. All grade II to IV gliomas and glioneuronal tumors showed increased AMT SUV, including all recurrent/residual tumors. Gadolinium enhancement on MRI was associated with high VD' values, suggesting impaired blood-brain barrier, while k'(3) values were not related to contrast enhancement. Low-grade astrocytic gliomas showed increased tryptophan metabolism, as measured by k'(3). In contrast, oligodendrogliomas showed high VD' values but lower k'(3) as compared with normal cortex. In astrocytic tumors, low grade was associated with high k'(3) and lower VD', while high-grade tumors showed the reverse pattern. The findings show high AMT uptake in primary and residual/recurrent gliomas and glioneuronal tumors. Increased AMT uptake can be due to increased metabolism of tryptophan and/or high volume of distribution, depending on tumor type and grade. High tryptophan metabolic rates in low-grade tumors may indicate activation of the kynurenine pathway, a mechanism regulating tumor cell growth. AMT PET might be a useful molecular imaging method to guide therapeutic approaches aimed at controlling tumor cell proliferation by acting on tryptophan metabolism.