Exploratory Clinical Trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for Imaging xC Transporter Using Positron Emission Tomography in Patients with Non-Small Cell Lung or Breast Cancer

Purpose: (4S)-4-(3-[F-18]fluoropropyl)-L-glutamate (BAY 94-9392, alias [F-18]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 [F-18]FSPG in patients relative to 2-[F-18]fluoro-2-deoxyglucose ([F-18]FDG). The correlation of [F-18]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 [F-18]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq[F-18]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody. Results: [F-18] FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [F-18]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [F-18] FSPG detected 59 of 67 (88%) [F-18]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [F-18] FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [F-18]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [F-18] FSPG correlated significantly with the intensity of immunohistochemical staining of x(C)(-) transporter and CD44 (P < 0.01). Conclusions: [F-18]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [F-18]FSPG PET may assess x(C)(-) transporter activity in patients with cancer. Clin Cancer Res; 18(19); 5427-37. (C)2012 AACR.