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

Background The PET tracer (4S)-4-(3-[¹⁸F]fluoropropyl)-l-glutamate (¹⁸F-FSPG) targets the system x_C^- 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 (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 ± 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 K_i 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.