Quantification of tryptophan transport and metabolism in lung tumors using PET.
Abnormal tryptophan metabolism catalyzed by indoleamine 2,3-dioxygenase may play a prominent role in tumor immunoresistance in many tumor types, including lung tumors. The goal of this study was to evaluate the in vivo kinetics of alpha-(11)C-methyl-l-tryptophan (AMT), a PET tracer for tryptophan metabolism, in human lung tumors.


METHODS
Tracer transport and metabolic rates were evaluated in 18 lesions of 10 patients using dynamic PET/CT with AMT. The kinetic values were compared between tumors and unaffected lung tissue, tested against a simplified analytic approach requiring no arterial blood sampling, and correlated with standardized uptake values (SUVs) obtained from (18)F-FDG PET/CT scans.


RESULTS
Most non-small cell lung cancers (NSCLCs) showed prolonged retention of AMT, but 3 other lesions (2 benign lesions and a rectal cancer metastasis) and unaffected lung tissue showed no such retention. Transport and metabolic rates of AMT were substantially higher in NSCLCs than in the other tumors and unaffected lung tissue. A simplified analytic approach provided an excellent estimate of transport rates but only suboptimal approximation of tryptophan metabolic rates. (18)F-FDG SUVs showed a positive correlation with AMT uptake, suggesting higher tryptophan transport and metabolism in tumors with higher proliferation rates.


CONCLUSIONS
Prolonged retention of AMT in NSCLCs suggests high metabolic rates of tryptophan in these tumors. AMT PET/CT may be a clinically useful molecular imaging method for personalized cancer treatment by identifying and monitoring patients who have increased tumor tryptophan metabolism and are potentially sensitive to immunopharmacotherapy with indoleamine 2,3-dioxygenase inhibitors.
Juhász
Csaba
C
PET Center, Children's Hospital of Michigan, Wayne State University, Detroit, Michigan, USA. juhasz@pet.wayne.edu
Muzik
Otto
O
Lu
Xin
X
Jahania
M Salik
MS
Soubani
Ayman O
AO
Khalaf
Majid
M
Peng
Fangyu
F
Mangner
Thomas J
TJ
Chakraborty
Pulak K
PK
Chugani
Diane C
DC
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D012004:Rectal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000556:secondary; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C020774:alpha-methyltryptophan; D014364:Tryptophan