TY - JOUR
T1 - In vivo PET assay of tumor glutamine flux and metabolism
T2 - In-human trial of 18f-(2S,4R)-4-fluoroglutamine
AU - Dunphy, Mark P.S.
AU - Harding, James J.
AU - Venneti, Sriram
AU - Zhang, Hanwen
AU - Burnazi, Eva M.
AU - Bromberg, Jacqueline
AU - Omuro, Antonio M.
AU - Hsieh, James J.
AU - Mellinghoff, Ingo K.
AU - Staton, Kevin
AU - Pressl, Christina
AU - Beattie, Bradley J.
AU - Zanzonico, Pat B.
AU - Gerecitano, John F.
AU - Kelsen, David P.
AU - Weber, Wolfgang
AU - Lyashchenko, Serge K.
AU - Kung, Hank F.
AU - Lewis, Jason S.
N1 - Funding Information:
Supported by the David Mahoney Neuroimaging Program of the Dana Foundation, the National Cancer Institute (grants P50 CA086438, R01 CA164490, R01 CA172546, and R21 CA167803), and Stand Up To Cancer (grant SU2C-AACR-DT0509). MSKCC core facilities are supported by a National Institutes of Health Cancer Center Support grant (grant P30 CA08748). Salary support provided by the National Cancer Institute (grants R21 CA167803 and R01 CA172546 to M.P.S.D.).
Funding Information:
Research was supported by a David Mahoney Neuroimaging Program grant of the Dana Foundation; a Stand Up to Cancer Dream Team translational research grant (grant SU2C-AACR-DT0509); and the National Institutes of Health–National Cancer Institute (grants P30 CA008748, P50 CA086438, R01 CA164490, R21 CA167803, and R01 CA172546). The authors had control of the data and information submitted for publication.
Publisher Copyright:
© RSNA, 2018.
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85046024861&partnerID=8YFLogxK
U2 - 10.1148/radiol.2017162610
DO - 10.1148/radiol.2017162610
M3 - Article
C2 - 29388903
AN - SCOPUS:85046024861
SN - 0033-8419
VL - 287
SP - 667
EP - 675
JO - Radiology
JF - Radiology
IS - 2
ER -