PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, MI 48201, USA.
Clin Nucl Med. 2012 Sep;37(9):838-42. doi: 10.1097/RLU.0b013e318251e458.
PET studies with α[C-11]methyl-L-tryptophan (AMT) have shown decreased serotonin synthesis based on a decrease of the unidirectional uptake rate (K-complex) in neuropsychiatric conditions such as autism and depression. Increased AMT K-complex in tumors can indicate increased tryptophan metabolism via the immunosuppressive kynurenine pathway. Moreover, apparent AMT volume of distribution (VD') reflects net tryptophan transport from blood to tissue. We evaluated if kinetic parameters (K-complex, VD') of AMT, measured by PET, can predict the proliferative activity of glioma, and if these AMT parameters are altered in the remote cortex.
We evaluated dynamic AMT PET images of 30 adult patients with grade 2 to 4 gliomas according to the World Health Organization's classification to determine tumoral AMT VD' and K-complex values, which were correlated with tumor proliferative activity as assessed by the Ki-67 labeling index in resected tumor specimens. We also compared cortical VD' and K-complex values between patients with glioma and healthy controls.
Both VD' and K-complex values were significantly higher in gliomas than in the contralateral cortex (VD', P < 0.001; K-complex, P < 0.001). Tumoral VD' values and tumor/cortex VD' ratios, but not the K-complex, showed strong positive correlations with the proliferative activity of glioma (P ≤ 0.001). The contralateral frontal cortex showed decreased AMT VD' and K-complex in patients with glioma compared with those in controls (P ≤ 0.01).
Increased net amino acid transport into tumor tissue, quantified by PET, can serve as an imaging marker of the proliferative activity of glioma. The data also suggest a glioma-induced down-regulation of cortical serotonin synthesis, likely mediated by shunting of tryptophan from serotonin synthesis to kynurenine metabolism.
采用 α[C-11]甲基-L-色氨酸（AMT）的 PET 研究显示，在自闭症和抑郁症等神经精神疾病中，由于单向摄取率（K 复合物）下降，导致血清素合成减少。肿瘤中 AMT K 复合物的增加表明色氨酸代谢通过免疫抑制犬尿氨酸途径增加。此外，表观 AMT 分布容积（VD'）反映了从血液到组织的净色氨酸转运。我们评估了 PET 测量的 AMT 动力学参数（K 复合物、VD'）是否可以预测胶质瘤的增殖活性，以及这些 AMT 参数是否在远隔皮质中发生改变。
我们评估了 30 名成人 2 至 4 级胶质瘤患者的动态 AMT PET 图像，以根据世界卫生组织的分类确定肿瘤 AMT VD'和 K 复合物值，并将其与切除肿瘤标本中的 Ki-67 标记指数评估的肿瘤增殖活性相关联。我们还比较了胶质瘤患者和健康对照组之间的皮质 VD'和 K 复合物值。
与对侧皮质相比，胶质瘤中的 VD'和 K 复合物值均显著升高（VD'，P <0.001；K 复合物，P <0.001）。肿瘤 VD'值和肿瘤/皮质 VD'比值与胶质瘤的增殖活性呈强正相关（P ≤ 0.001），但 K 复合物则不然。与对照组相比，胶质瘤患者的对侧额皮质的 AMT VD'和 K 复合物均降低（P ≤ 0.01）。
通过 PET 量化的肿瘤组织中净氨基酸转运的增加可作为胶质瘤增殖活性的成像标志物。数据还表明，胶质瘤诱导的皮质血清素合成下调，可能是由色氨酸从血清素合成转向犬尿氨酸代谢的分流介导的。
