Imaging, Diagnosis, Prognosis Exploratory Clinical Trial of (4S)-4-(3-[F]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]fluoropropyl)-L-glutamate (BAY 94-9392, alias [F]FSPG) is a new tracer to image xC transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [F]FSPG in patients relative to 2-[F]fluoro-2-deoxyglucose ([F]FDG). The correlation of [F]FSPG uptake with immunohistochemical expression of xC transporter and CD44, which stabilizes the xCT subunit of system xC , was also analyzed. ExperimentalDesign:Patients with non–small cell lung cancer (NSCLC, n1⁄4 10) or breast cancer (n1⁄4 5) who had a positive [F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300MBq [F]FSPG. Immunohistochemistrywas done using xCTand CD44-specific antibody. Results: [F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [F]FSPG detected 59 of 67 (88%) [F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [F]FSPG correlated significantly with the intensity of immunohistochemical staining of xC transporter and CD44 (P < 0.01). Conclusions: [F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [F]FSPG PETmay assess xC transporter activity in patients with cancer.Clin Cancer Res; 18(19); 5427–37. 2012 AACR.