In vivo uptake and metabolism of alpha-[11C]methyl-L-tryptophan in human brain tumors.
Abnormal metabolism of tryptophan has been implicated in modulation of tumor cell proliferation and immunoresistance. alpha-[(11)C]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.
Juhász
Csaba
C
Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Detroit Medical Center, Wayne State University School of Medicine, 48201, USA. juhasz@pet.wayne.edu
Chugani
Diane C
DC
Muzik
Otto
O
Wu
Dafang
D
Sloan
Andrew E
AE
Barger
Geoffrey
G
Watson
Craig
C
Shah
Aashit K
AK
Sood
Sandeep
S
Ergun
Eser L
EL
Mangner
Tom J
TJ
Chakraborty
Pulak K
PK
Kupsky
William J
WJ
Chugani
Harry T
HT
D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography / Q000379:methods / Q000592:standards; D005260:Female; D005682:Gadolinium; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000592:standards; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography / Q000379:methods / Q000592:standards; D012640:Seizures / Q000378:metabolism; D012680:Sensitivity and Specificity; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000592:standards
D002250:Carbon Radioisotopes; C020774:alpha-methyltryptophan; D014364:Tryptophan; D005682:Gadolinium; D005947:Glucose