In vivo PET assay of tumor glutamine flux and metabolism: In-human trial of (18)F-(2S,4R)-4-fluoroglutamine Journal Article

Authors: Dunphy, M. P. S.; Harding, J. J.; Venneti, S.; Zhang, H.; Burnazi, E. M.; Bromberg, J.; Omuro, A. M.; Hsieh, J. J.; Mellinghoff, I. K.; Staton, K.; Pressl, C.; Beattie, B. J.; Zanzonico, P. B.; Gerecitano, J. F.; Kelsen, D. P.; Weber, W.; Lyashchenko, S. K.; Kung, H. F.; Lewis, J. S.
Article Title: In vivo PET assay of tumor glutamine flux and metabolism: In-human trial of (18)F-(2S,4R)-4-fluoroglutamine
Abstract: Purpose: To assess the clinical safety, pharmacokinetics, and tumor imaging characteristics of fluorine 18-(2S,4R)-4-fluoroglutamine (FGln), a glutamine analog radiologic imaging agent. Materials and Methods: This study was approved by the institutional review board and conducted under a U.S. Food and Drug Administration-approved Investigational New Drug application in accordance with the Helsinki Declaration and the Health Insurance Portability and Accountability Act. All patients provided written informed consent. Between January 2013 and October 2016, 25 adult patients with cancer received an intravenous bolus of FGln tracer (mean, 244 MBq ± 118, <100 μg) followed by positron emission tomography (PET) and blood radioassays. Patient data were summarized with descriptive statistics. FGln biodistribution and plasma amino acid levels in nonfasting patients (n = 13) were compared with those from patients who fasted at least 8 hours before injection (n = 12) by using nonparametric one-way analysis of variance with Bonferroni correction. Tumor FGln avidity versus fluorodeoxyglucose (FDG) avidity in patients with paired PET scans (n = 15) was evaluated with the Fisher exact test. P <.05 was considered indicative of a statistically significant difference. Results: FGln PET depicted tumors of different cancer types (breast, pancreas, renal, neuroendocrine, lung, colon, lymphoma, bile duct, or glioma) in 17 of the 25 patients, predominantly clinically aggressive tumors with genetic mutations implicated in abnormal glutamine metabolism. Acute fasting had no significant effect on FGln biodistribution and plasma amino acid levels. FGln-avid tumors were uniformly FDG-avid but not vice versa (P =.07). Patients experienced no adverse effects. Conclusion: Preliminary human FGln PET trial results provide clinical validation of abnormal glutamine metabolism as a potential tumor biomarker for targeted radiotracer imaging in several different cancer types. © RSNA, 2018.
Keywords: adult; clinical article; controlled study; aged; middle aged; young adult; unclassified drug; gene mutation; somatic mutation; clinical trial; drug safety; united states; united states food and drug administration; positron emission tomography; neoplasm; neoplasms; metabolism; gene amplification; tumor volume; food and drug administration; drug effect; pathology; validation study; diagnostic imaging; protein p53; tumor marker; cell transformation, neoplastic; adverse outcome; drug distribution; tissue distribution; cell transformation; cyclin dependent kinase inhibitor 1b; positron-emission tomography; drug clearance; single drug dose; open study; amino acid blood level; drug metabolism; phase 1 clinical trial; drug cytotoxicity; cyclin dependent kinase inhibitor 2a; fluorine 18; radioisotope decay; glutamine; tumor diagnosis; amino acid transport; correlational study; notch1 receptor; isocitrate dehydrogenase; succinate dehydrogenase; descriptive research; fluorine radioisotopes; fluorine; radioassay; 4 fluoroglutamine f 18; humans; human; male; female; priority journal; article; analogs and derivatives; biomarkers, tumor; 4-fluoroglutamine
Journal Title: Radiology
Volume: 287
Issue: 2
ISSN: 0033-8419
Publisher: Radiological Society of North America, Inc.  
Date Published: 2018-05-01
Start Page: 667
End Page: 675
Language: English
DOI: 10.1148/radiol.2017162610
PUBMED: 29388903
PROVIDER: scopus
PMCID: PMC5929369
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Jacqueline Bromberg
    104 Bromberg
  2. James Joseph Harding
    66 Harding
  3. Antonio Marcilio Padula Omuro
    176 Omuro
  4. Mark Phillip Dunphy
    48 Dunphy
  5. Eva M Burnazi
    13 Burnazi
  6. Pat B Zanzonico
    246 Zanzonico
  7. James J Hsieh
    114 Hsieh
  8. Hanwen Zhang
    29 Zhang
  9. Jason S Lewis
    242 Lewis
  10. David P Kelsen
    332 Kelsen
  11. Bradley Beattie
    106 Beattie
  12. Wolfgang Andreas Weber
    147 Weber
  13. Kevin David Staton
    6 Staton