(4S)-4-(3-18F-fluoropropyl)-L-glutamate for imaging of x c- transporter activity in hepatocellular carcinoma using PET: Preclinical and exploratory clinical studies

Abstract

(4S)-4-(3-18F-fluoropropyl)-L-glutamate (18F-FSPG, or BAY 94-9392) is a new tracer to assess system xC- transporter activity with PET. The aim of this study was to explore the tumor detection rate of 18F-FSPG, compared with that of 18F-FDG, in patients with hepatocellular carcinoma (HCC). Methods: Preclinically, in vivo HCC models of orthotopically implanted Huh7 and MH3924a cancer cells were studied with 18F-FSPG in Naval Medical Research Institute nude mice (n = 3) and August-Copenhagen Irish rats (n = 4), respectively. Clinically, 5 patients with HCC who had hyper- or isometabolic lesions on 18F-FDG PET were enrolled for evaluation of the tracer. Dynamic whole-body PET images with 18F-FSPG were acquired for up to 120 min after injection of approximately 300 MBq of 18F-FSPG. Immunohistochemical expression levels of the xCT subunit of the system xC- and CD44 of HCC were studied in 4 patients with HCC. Results: Strong tumor uptake and low background from nontarget tissue allowed excellent tumor visualization in animal models with orthotopically implanted liver tumors. 18F-FSPG PET procedures were well tolerated in all patients. 18F-FSPG PET and 18F-FDG detected lesions in 5 of 5 and 3 of 5 patients, respectively. The maximal standardized uptake values (SUV) were comparable ( 18F-FSPG, 4.7 ± 3.2; 18F-FDG, 6.1 ± 2.9). The ratios of maximal SUV of the tumor to mean SUV of normal liver were also comparable (18F-FSPG, 3.6 ± 2.2; 18F-FDG, 2.7 ± 1.3), but the mean SUV of normal liver of 18F-FSPG was significantly lower than that of 18F-FDG (P < 0.05). Two patients with HCC who showed both xCT and CD44 expression had moderate or intense accumulation of 18F-FSPG, but the remaining 2 patients with negative CD44 expression showed mild uptake. Conclusion: 18F-FSPG was successfully translated from preclinical evaluation into patients with HCC. 18F-FSPG may be a promising tumor PET agent with a high cancer detection rate in patients with HCC. COPYRIGHT © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.