Exploratory clinical trial of (4S)-4-(3-[¹⁸F]fluoropropyl)-L- glutamate for imaging x_C^- transporter using positron emission tomography in patients with non-small cell lung or breast cancer

Purpose: (4S)-4-(3-[¹⁸F]fluoropropyl)-L-glutamate (BAY 94-9392, alias [¹⁸F]FSPG) is a new tracer to image x_C^- transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [¹⁸F]FSPG in patients relative to 2-[¹⁸F]fluoro-2-deoxyglucose ([¹⁸F]FDG). The correlation of [¹⁸F]FSPG uptake with immunohistochemical expression of x _C^- transporter and CD44, which stabilizes the xCT subunit of system x_C^-, was also analyzed. Experimental Design: Patients with non-small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [¹⁸F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq[¹⁸F]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody. Results: [¹⁸F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [¹⁸F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [¹⁸F]FSPG detected 59 of 67 (88%) [ ¹⁸F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [¹⁸F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [¹⁸F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [ ¹⁸F]FSPG correlated significantly with the intensity of immunohistochemical staining of x_C^- transporter and CD44 (P < 0.01). Conclusions: [¹⁸F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [ ¹⁸F]FSPG PET may assess x_C^- transporter activity in patients with cancer.