Assessment of tryptophan uptake and kinetics using 1-(2-18F-fluoroethyl)-L-tryptophan and α-11C-methyl-L-tryptophan PET imaging in mice implanted with patient-derived brain tumor xenografts

Sharon K. Michelhaugh, Otto Muzik, Anthony R. Guastella, Neil V. Klinger, Lisa A. Polin, Hancheng Cai, Yangchun Xin, Thomas J. Mangner, Shaohui Zhang, Csaba Juhász, Sandeep Mittal

Research output: Contribution to journalArticle

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Abstract

Abnormal tryptophan metabolism via the kynurenine pathway is involved in the pathophysiology of a variety of human diseases including cancers. α-11C-methyl-L-tryptophan (11C-AMT) PET imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of 11C limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-18F-fluoroethyl)-L-tryptophan (18F-FETrp) may be useful to assess tryptophan metabolism via the kynurenine pathway. In this study, we tested in vivo organ and tumor uptake and kinetics of 18F-FETrp in patient-derived xenograft mouse models and compared them with 11C-AMT uptake. Methods: Xenograft mouse models of glioblastoma and metastatic brain tumors (from lung and breast cancer) were developed by subcutaneous implantation of patient tumor fragments. Dynamic PET scans with 18F-FETrp and 11C-AMT were obtained for mice bearing human brain tumors 1-7 d apart. The biodistribution and tumoral SUVs for both tracers were compared. Results: 18F-FETrp showed prominent uptake in the pancreas and no bone uptake, whereas 11C-AMT showed higher uptake in the kidneys. Both tracers showed uptake in the xenograft tumors, with a plateau of approximately 30 min after injection; however, 18F-FETrp showed higher tumoral SUV than 11C-AMT in all 3 tumor types tested. The radiation dosimetry for 18F-FETrp determined from the mouse data compared favorably with the clinical 18F-FDG PET tracer. Conclusion: 18F-FETrp tumoral uptake, biodistribution, and radiation dosimetry data provide strong preclinical evidence that this new radiotracer warrants further studies that may lead to a broadly applicable molecular imaging tool to examine abnormal tryptophan metabolism in human tumors.

Original languageEnglish (US)
Pages (from-to)208-213
Number of pages6
JournalJournal of Nuclear Medicine
Volume58
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

Heterografts
Brain Neoplasms
Tryptophan
Radiometry
Kynurenine
Neoplasms
tryptophan methyl ester
Molecular Imaging
Fluorodeoxyglucose F18
Glioblastoma
Positron-Emission Tomography
Half-Life
Pancreas
Lung Neoplasms
Breast Neoplasms
Kidney
Bone and Bones
Injections

Keywords

  • Brain metastasis
  • Glioblastoma
  • Indoleamine 2,3- dioxygenase

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Assessment of tryptophan uptake and kinetics using 1-(2-18F-fluoroethyl)-L-tryptophan and α-11C-methyl-L-tryptophan PET imaging in mice implanted with patient-derived brain tumor xenografts. / Michelhaugh, Sharon K.; Muzik, Otto; Guastella, Anthony R.; Klinger, Neil V.; Polin, Lisa A.; Cai, Hancheng; Xin, Yangchun; Mangner, Thomas J.; Zhang, Shaohui; Juhász, Csaba; Mittal, Sandeep.

In: Journal of Nuclear Medicine, Vol. 58, No. 2, 01.02.2017, p. 208-213.

Research output: Contribution to journalArticle

Michelhaugh, Sharon K. ; Muzik, Otto ; Guastella, Anthony R. ; Klinger, Neil V. ; Polin, Lisa A. ; Cai, Hancheng ; Xin, Yangchun ; Mangner, Thomas J. ; Zhang, Shaohui ; Juhász, Csaba ; Mittal, Sandeep. / Assessment of tryptophan uptake and kinetics using 1-(2-18F-fluoroethyl)-L-tryptophan and α-11C-methyl-L-tryptophan PET imaging in mice implanted with patient-derived brain tumor xenografts. In: Journal of Nuclear Medicine. 2017 ; Vol. 58, No. 2. pp. 208-213.
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abstract = "Abnormal tryptophan metabolism via the kynurenine pathway is involved in the pathophysiology of a variety of human diseases including cancers. α-11C-methyl-L-tryptophan (11C-AMT) PET imaging demonstrated increased tryptophan uptake and trapping in epileptic foci and brain tumors, but the short half-life of 11C limits its widespread clinical application. Recent in vitro studies suggested that the novel radiotracer 1-(2-18F-fluoroethyl)-L-tryptophan (18F-FETrp) may be useful to assess tryptophan metabolism via the kynurenine pathway. In this study, we tested in vivo organ and tumor uptake and kinetics of 18F-FETrp in patient-derived xenograft mouse models and compared them with 11C-AMT uptake. Methods: Xenograft mouse models of glioblastoma and metastatic brain tumors (from lung and breast cancer) were developed by subcutaneous implantation of patient tumor fragments. Dynamic PET scans with 18F-FETrp and 11C-AMT were obtained for mice bearing human brain tumors 1-7 d apart. The biodistribution and tumoral SUVs for both tracers were compared. Results: 18F-FETrp showed prominent uptake in the pancreas and no bone uptake, whereas 11C-AMT showed higher uptake in the kidneys. Both tracers showed uptake in the xenograft tumors, with a plateau of approximately 30 min after injection; however, 18F-FETrp showed higher tumoral SUV than 11C-AMT in all 3 tumor types tested. The radiation dosimetry for 18F-FETrp determined from the mouse data compared favorably with the clinical 18F-FDG PET tracer. Conclusion: 18F-FETrp tumoral uptake, biodistribution, and radiation dosimetry data provide strong preclinical evidence that this new radiotracer warrants further studies that may lead to a broadly applicable molecular imaging tool to examine abnormal tryptophan metabolism in human tumors.",
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AU - Michelhaugh, Sharon K.

AU - Muzik, Otto

AU - Guastella, Anthony R.

AU - Klinger, Neil V.

AU - Polin, Lisa A.

AU - Cai, Hancheng

AU - Xin, Yangchun

AU - Mangner, Thomas J.

AU - Zhang, Shaohui

AU - Juhász, Csaba

AU - Mittal, Sandeep

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