Abstract
(4S)-4-(3-[(18)F]fluoropropyl)-l-glutamate (BAY 94-9392, alias [(18)F]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 [(18)F]FSPG in patients relative to 2-[(18)F]fluoro-2-deoxyglucose ([(18)F]FDG). The correlation of [(18)F]FSPG uptake with immunohistochemical expression of x(C)(-) transporter and CD44, which stabilizes the xCT subunit of system x(C)(-), was also analyzed. Patients with non-small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [(18)F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq [(18)F]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody. [(18)F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [(18)F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [(18)F]FSPG detected 59 of 67 (88%) [(18)F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [(18)F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [(18)F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [(18)F]FSPG correlated significantly with the intensity of immunohistochemical staining of x(C)(-) transporter and CD44 (P < 0.01). [(18)F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [(18)F]FSPG PET may assess x(C)(-) transporter activity in patients with cancer.
Highlights
One of the hallmarks of cancer is reprogramming energy metabolism [1]
Increased glucose uptake and enhanced glycolytic metabolism of tumors is used for tumor positron emission tomography (PET) imaging with 2[18F]fluoro-2-deoxyglucose ([18F]FDG)
Patients and [18F]FSPG positron emission tomography/computed tomography (PET/CT) procedure Among patients assessed for eligibility, 1 patient with
Summary
One of the hallmarks of cancer is reprogramming energy metabolism [1]. Cancer cells use both glucose and glutamine as a substrate to generate energy and to provide building blocks, such as amino acids, nucleosides, and Authors' Affiliations: Departments of 1Nuclear Medicine, 2Pulmonology, 3Surgery, and 4Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 5Bayer Pharma AG, Bayer Healthcare Pharmaceuticals; 6Piramal Imaging, Berlin, Germany; 7Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics; and 8Departments of Bioengineering and Materials Science & Engineering, Stanford University, Stanford, CaliforniaNote: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).Ó2012 American Association for Cancer Research.fatty acids [2,3,4]. One of the hallmarks of cancer is reprogramming energy metabolism [1]. Cancer cells use both glucose and glutamine as a substrate to generate energy and to provide building blocks, such as amino acids, nucleosides, and Authors' Affiliations: Departments of 1Nuclear Medicine, 2Pulmonology, 3Surgery, and 4Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 5Bayer Pharma AG, Bayer Healthcare Pharmaceuticals; 6Piramal Imaging, Berlin, Germany; 7Molecular Imaging Program, Department of Radiology, Stanford Hospital and Clinics; and 8Departments of Bioengineering and Materials Science & Engineering, Stanford University, Stanford, California. Increased glucose uptake and enhanced glycolytic metabolism of tumors is used for tumor positron emission tomography (PET) imaging with 2[18F]fluoro-2-deoxyglucose ([18F]FDG). Imaging of other fundamental processes in tumors would be of great interest for early cancer detection, therapy monitoring, or prediction of resistance to chemotherapy [5]
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