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 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2018 -- Source: Scopus |
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