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