Quantification of tryptophan transport and metabolism in lung tumors using PET

Csaba Juhász, Otto Muzik, Xin Lu, M. Salik Jahania, Ayman O. Soubani, Majid Khalaf, Fangyu Peng, Thomas J. Mangner, Pulak K. Chakraborty, Diane C. Chugani

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 α- 11C-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 18F-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. 18F-FDG SUVs showed a positive correlation with AMT uptake, suggesting higher tryptophan transport and metabolism in tumors with higher proliferation rates. Conclusion: 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. COPY

Original languageEnglish (US)
Pages (from-to)356-363
Number of pages8
JournalJournal of Nuclear Medicine
Volume50
Issue number3
DOIs
StatePublished - Mar 1 2009

Fingerprint

Tryptophan
Lung
Neoplasms
Non-Small Cell Lung Carcinoma
Indoleamine-Pyrrole 2,3,-Dioxygenase
Fluorodeoxyglucose F18
Molecular Imaging
Physiologic Monitoring
Rectal Neoplasms
Neoplasm Metastasis

Keywords

  • 2-deoxy-2-[ f]fluoro-D-glucose
  • Lung tumors
  • Metabolism
  • Positron emission tomography
  • Tryptophan

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Juhász, C., Muzik, O., Lu, X., Jahania, M. S., Soubani, A. O., Khalaf, M., ... Chugani, D. C. (2009). Quantification of tryptophan transport and metabolism in lung tumors using PET. Journal of Nuclear Medicine, 50(3), 356-363. https://doi.org/10.2967/jnumed.108.058776

Quantification of tryptophan transport and metabolism in lung tumors using PET. / Juhász, Csaba; Muzik, Otto; Lu, Xin; Jahania, M. Salik; Soubani, Ayman O.; Khalaf, Majid; Peng, Fangyu; Mangner, Thomas J.; Chakraborty, Pulak K.; Chugani, Diane C.

In: Journal of Nuclear Medicine, Vol. 50, No. 3, 01.03.2009, p. 356-363.

Research output: Contribution to journalArticle

Juhász, C, Muzik, O, Lu, X, Jahania, MS, Soubani, AO, Khalaf, M, Peng, F, Mangner, TJ, Chakraborty, PK & Chugani, DC 2009, 'Quantification of tryptophan transport and metabolism in lung tumors using PET', Journal of Nuclear Medicine, vol. 50, no. 3, pp. 356-363. https://doi.org/10.2967/jnumed.108.058776
Juhász, Csaba ; Muzik, Otto ; Lu, Xin ; Jahania, M. Salik ; Soubani, Ayman O. ; Khalaf, Majid ; Peng, Fangyu ; Mangner, Thomas J. ; Chakraborty, Pulak K. ; Chugani, Diane C. / Quantification of tryptophan transport and metabolism in lung tumors using PET. In: Journal of Nuclear Medicine. 2009 ; Vol. 50, No. 3. pp. 356-363.
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AU - Khalaf, Majid

AU - Peng, Fangyu

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N2 - 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 α- 11C-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 18F-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. 18F-FDG SUVs showed a positive correlation with AMT uptake, suggesting higher tryptophan transport and metabolism in tumors with higher proliferation rates. Conclusion: 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. COPY

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