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. Clin Cancer Res; 18(19); 5427–37. ©2012 AACR.