18F-FSPG PET/CT Imaging of System xC2 Transporter Activity in Patients with Primary and Metastatic Brain Tumors

Mirwais Wardak, Ida Sonni, Audrey P. Fan, Ryogo Minamimoto, Mehran Jamali, Negin Hatami, Greg Zaharchuk, Nancy Fischbein, Seema Nagpal, Gordon Li, Norman Koglin, Mathias Berndt, Santiago Bullich, Andrew W. Stephens, Ludger M. Dinkelborg, Ty Abel, H. Charles Manning, Jarrett Rosenberg, Frederick T. Chin, Sanjiv Sam GambhirErik S. Mittra

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1 Scopus citations


Background: The PET tracer (4S)-4-(3-[18F]fluoropropyl)-l-glutamate (18F-FSPG) targets the system xC cotransporter, which is over-expressed 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 6 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 (ClinicalTrials.gov 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 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.

Original languageEnglish (US)
Pages (from-to)620-631
Number of pages12
Issue number3
StatePublished - Jun 2022
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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