Dataset Information

Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and ?-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts.

ABSTRACT: Abnormal tryptophan metabolism via the kynurenine pathway is involved in the pathophysiology of a variety of human diseases including cancers. ?-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.

SUBMITTER: Michelhaugh SK

PROVIDER: S-EPMC5288739 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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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 SK Muzik Otto O Guastella Anthony R AR Klinger Neil V NV Polin Lisa A LA Cai Hancheng H Xin Yangchun Y Mangner Thomas J TJ Zhang Shaohui S Juhász Csaba C Mittal Sandeep S

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20161020 2

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 (<su ...[more]

PMID: 27765857

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