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18F-FSPG PET/CT Imaging of System xC- Transporter Activity in Patients with Primary and Metastatic Brain Tumors.

  • Wardak, Mirwais1
  • Sonni, Ida1
  • Fan, Audrey P1
  • Minamimoto, Ryogo1
  • Jamali, Mehran1
  • Hatami, Negin1
  • Zaharchuk, Greg1
  • Fischbein, Nancy1
  • Nagpal, Seema1
  • Li, Gordon1
  • Koglin, Norman1
  • Berndt, Mathias1
  • Bullich, Santiago1
  • Stephens, Andrew W1
  • Dinkelborg, Ludger M1
  • Abel, Ty1
  • Manning, H Charles1
  • Rosenberg, Jarrett1
  • Chin, Frederick T1
  • Gambhir, Sanjiv Sam1
  • And 1 more
  • 1 From the Department of Radiology, Molecular Imaging Program at Stanford (MIPS) (M.W., I.S., A.P.F., R.M., M.J., N.H., G.Z., N.F., J.R., F.T.C., S.S.G., E.S.M.), Department of Neurosurgery (N.F., S.N., G.L.), and Department of Neurology and Neurological Sciences (N.F., S.N., G.L.), Stanford University School of Medicine, Stanford, Calif; Department of Molecular and Medical Pharmacology, UCLA Ahmanson Biological Imaging Center, David Geffen School of Medicine at UCLA, Los Angeles, Calif (I.S.); Department of Biomedical Engineering, Department of Neurology, University of California, Davis, Davis, Calif (A.P.F.); Stanford Bio-X (M.W., G.Z., G.L., F.T.C., S.S.G.) and Departments of Bioengineering (S.S.G.) and Materials Science & Engineering (S.S.G.), Stanford University, Stanford, Calif; Life Molecular Imaging GmbH, Berlin, Germany (N.K., M.B., S.B., A.W.S., L.M.D.); Department of Pathology, Microbiology and Immunology (T.A.) and Department of Radiology and Radiological Sciences, Institute of Imaging Science, Center for Molecular Probes (H.C.M.), Vanderbilt University Medical Center, Nashville, Tenn; and Department of Cancer Systems Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Tex (H.C.M.). , (Germany)
Published Article
Radiological Society of North America
Publication Date
Jun 01, 2022
DOI: 10.1148/radiol.203296
PMID: 35191738


Background The PET tracer (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (18F-FSPG) targets the system xC- cotransporter, which is overexpressed in various tumors. Purpose To assess the role of 18F-FSPG PET/CT in intracranial malignancies. Materials and Methods Twenty-six patients (mean age, 54 years ± 12; 17 men; 48 total lesions) with primary brain tumors (n = 17) or brain metastases (n = 9) were enrolled in this prospective, single-center study ( identifier: NCT02370563) between November 2014 and March 2016. A 30-minute dynamic brain 18F-FSPG PET/CT scan and a static whole-body (WB) 18F-FSPG PET/CT scan at 60-75 minutes were acquired. Moreover, all participants underwent MRI, and four participants underwent fluorine 18 (18F) fluorodeoxyglucose (FDG) PET imaging. PET parameters and their relative changes were obtained for all lesions. Kinetic modeling was used to estimate the 18F-FSPG tumor rate constants using the dynamic and dynamic plus WB PET data. Imaging parameters were correlated to lesion outcomes, as determined with follow-up MRI and/or pathologic examination. The Mann-Whitney U test or Student t test was used for group mean comparisons. Receiver operating characteristic curve analysis was used for performance comparison of different decision measures. Results 18F-FSPG PET/CT helped identify all 48 brain lesions. The mean tumor-to-background ratio (TBR) on the whole-brain PET images at the WB time point was 26.6 ± 24.9 (range: 2.6-150.3). When 18F-FDG PET was performed, 18F-FSPG permitted visualization of non-18F-FDG-avid lesions or allowed better lesion differentiation from surrounding tissues. In participants with primary brain tumors, the predictive accuracy of the relative changes in influx rate constant Ki and maximum standardized uptake value to discriminate between poor and good lesion outcomes were 89% and 81%, respectively. There were significant differences in the 18F-FSPG uptake curves of lesions with good versus poor outcomes in the primary brain tumor group (P < .05) but not in the brain metastases group. Conclusion PET/CT imaging with (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (18F-FSPG) helped detect primary brain tumors and brain metastases with a high tumor-to-background ratio. Relative changes in 18F-FSPG uptake with multi-time-point PET appear to be helpful in predicting lesion outcomes. Clinical trial registration no. NCT02370563 © RSNA, 2022 Online supplemental material is available for this article.

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