PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: M Leyton; H Okazawa; M Diksic; J Paris; P Rosa; S Mzengeza; S N Young; P Blier; C Benkelfat Journal: Am J Psychiatry Date: 2001-05 Impact factor: 18.112
Authors: Csaba Juhász; Otto Muzik; Diane C Chugani; Harry T Chugani; Sandeep Sood; Pulak K Chakraborty; Geoffrey R Barger; Sandeep Mittal Journal: J Neurooncol Date: 2010-07-30 Impact factor: 4.130
Authors: Bálint Alkonyi; Sandeep Mittal; Ian Zitron; Diane C Chugani; William J Kupsky; Otto Muzik; Harry T Chugani; Sandeep Sood; Csaba Juhász Journal: J Neurooncol Date: 2011-11-03 Impact factor: 4.130
Authors: Edit Bosnyák; Sharon K Michelhaugh; Neil V Klinger; David O Kamson; Geoffrey R Barger; Sandeep Mittal; Csaba Juhász Journal: Clin Nucl Med Date: 2017-05 Impact factor: 7.794
Authors: David O Kamson; Tiffany J Lee; Kaushik Varadarajan; Natasha L Robinette; Otto Muzik; Pulak K Chakraborty; Michael Snyder; Geoffrey R Barger; Sandeep Mittal; Csaba Juhász Journal: J Nucl Med Date: 2014-09-04 Impact factor: 10.057
Authors: David O Kamson; Csaba Juhász; Amy Buth; William J Kupsky; Geoffrey R Barger; Pulak K Chakraborty; Otto Muzik; Sandeep Mittal Journal: J Neurooncol Date: 2013-01-09 Impact factor: 4.130
Authors: David O Kamson; Sandeep Mittal; Natasha L Robinette; Otto Muzik; William J Kupsky; Geoffrey R Barger; Csaba Juhász Journal: Neuro Oncol Date: 2014-03-26 Impact factor: 12.300
Authors: Edit Bosnyák; David O Kamson; Anthony R Guastella; Kaushik Varadarajan; Natasha L Robinette; William J Kupsky; Otto Muzik; Sharon K Michelhaugh; Sandeep Mittal; Csaba Juhász Journal: Neuro Oncol Date: 2015-06-18 Impact factor: 12.300
Authors: David O Kamson; Sandeep Mittal; Amy Buth; Otto Muzik; William J Kupsky; Natasha L Robinette; Geoffrey R Barger; Csaba Juhász Journal: Mol Imaging Date: 2013 Jul-Aug Impact factor: 4.488