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

Sora Baek, Chang Min Choi, Sei Hyun Ahn, Jong Won Lee, Gyungyub Gong, Jin Sook Ryu, Seung Jun Oh, Claudia Bacher-Stier, Lüder Fels, Norman Koglin, Christina Hultsch, Christoph A. Schatz, Ludger M. Dinkelborg, Erik S. Mittra, Sanjiv S. Gambhir, Dae Hyuk Moon

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67 Scopus citations

Abstract

Purpose: (4S)-4-(3-[18F]fluoropropyl)-L-glutamate (BAY 94-9392, alias [18F]FSPG) is a new tracer to image xC- 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 xC-, 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 xC- 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 xC- transporter activity in patients with cancer.

Original languageEnglish (US)
Pages (from-to)5427-5437
Number of pages11
JournalClinical Cancer Research
Volume18
Issue number19
DOIs
StatePublished - Oct 1 2012

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Baek, S., Choi, C. M., Ahn, S. H., Lee, J. W., Gong, G., Ryu, J. S., Oh, S. J., Bacher-Stier, C., Fels, L., Koglin, N., Hultsch, C., Schatz, C. A., Dinkelborg, L. M., Mittra, E. S., Gambhir, S. S., & Moon, D. H. (2012). 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. Clinical Cancer Research, 18(19), 5427-5437. https://doi.org/10.1158/1078-0432.CCR-12-0214