In VivoUptake and Metabolism of α-[11C]Methyl-l -Tryptophan in Human Brain Tumors
| Autor: | Aashit Shah, William J. Kupsky, Otto Muzik, Craig Watson, Sandeep Sood, Andrew E. Sloan, Tom J Mangner, Pulak K. Chakraborty, Dafang Wu, Diane C. Chugani, Harry T. Chugani, Geoffrey Barger, Eser Lay Ergun, Csaba Juhász |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male medicine.medical_specialty Kynurenine pathway Adolescent Gadolinium Biology Blood–brain barrier Sensitivity and Specificity Seizures In vivo Internal medicine Glioma medicine Humans Carbon Radioisotopes Child Aged Neoplasm Staging Cerebral Cortex Volume of distribution Brain Neoplasms Tryptophan Infant Electroencephalography Human brain Middle Aged medicine.disease Magnetic Resonance Imaging Glucose medicine.anatomical_structure Endocrinology Neurology Cerebral blood flow Child Preschool Positron-Emission Tomography Female Neurology (clinical) Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 26:345-357 |
| ISSN: | 1559-7016 0271-678X |
| Popis: | Abnormal metabolism of tryptophan has been implicated in modulation of tumor cell proliferation and immunoresistance. α-[11C]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'3values 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'3as compared with normal cortex. In astrocytic tumors, low grade was associated with high k'3and 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. |
| Databáze: | OpenAIRE |
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