title: 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.
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 of11C 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 of18F-FETrp in patient-derived xenograft mouse models and compared them with11C-AMT uptake.
  
  
  
  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 with18F-FETrp and11C-AMT were obtained for mice bearing human brain tumors 1-7 d apart. The biodistribution and tumoral SUVs for both tracers were compared.
  
  
  
  18F-FETrp showed prominent uptake in the pancreas and no bone uptake, whereas11C-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 than11C-AMT in all 3 tumor types tested. The radiation dosimetry for18F-FETrp determined from the mouse data compared favorably with the clinical18F-FDG PET tracer.
  
  
  
  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.
authors.affiliation: Department of Neurosurgery, Wayne State University, Detroit, Michigan.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Michelhaugh
authors.affiliation: Department of Pediatrics, Wayne State University, Detroit, Michigan.|Department of Radiology, Wayne State University, Detroit, Michigan.|PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan.
authors.forename: Otto
authors.initials: O
authors.lastname: Muzik
authors.affiliation: Department of Neurosurgery, Wayne State University, Detroit, Michigan.|Department of Oncology, Wayne State University, Detroit, Michigan.|Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Guastella
authors.affiliation: Department of Neurosurgery, Wayne State University, Detroit, Michigan.
authors.forename: Neil V
authors.initials: NV
authors.lastname: Klinger
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan.|Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Polin
authors.affiliation: Department of Radiology and Advanced Imaging Research Center, University of Texas Southwestern, Dallas, Texasand.
authors.forename: Hancheng
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Radiology and Advanced Imaging Research Center, University of Texas Southwestern, Dallas, Texasand.
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Department of Radiology, Wayne State University, Detroit, Michigan.|PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Mangner
authors.affiliation: PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Wayne State University, Detroit, Michigan.|PET Center and Translational Imaging Laboratory, Children's Hospital of Michigan, Detroit, Michigan.|Karmanos Cancer Institute, Detroit, Michigan.|Department of Neurology, Wayne State University, Detroit, Michigan.
authors.forename: Csaba
authors.initials: C
authors.lastname: Juhász
authors.affiliation: Department of Neurosurgery, Wayne State University, Detroit, Michigan smittal@med.wayne.edu.|Department of Oncology, Wayne State University, Detroit, Michigan.|Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Mittal
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D057054:Molecular Imaging / Q000379:methods*; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014364:Tryptophan / Q000493:pharmacokinetics*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D014408:Biomarkers, Tumor; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; C545932:(18F)fluoroethyltyrosine; D014443:Tyrosine; D014364:Tryptophan
keywords: brain metastasis; glioblastoma; indoleamine 2,3-dioxygenase