Sora Baek

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.

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 xC− 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. Clin Cancer Res; 18(19); 5427–37. ©2012 AACR.

(4S)-4-(3-18F-Fluoropropyl)-l-Glutamate for Imaging of xC¯ Transporter Activity in Hepatocellular Carcinoma Using PET: Preclinical and Exploratory Clinical Studies

(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.

FDG-PET as a Potential Tool for Selecting Patients with Advanced Non–Small Cell Lung Cancer Who May Be Spared Maintenance Therapy after First-Line Chemotherapy

Purpose: To investigate whether 18F-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) may be a potential tool to select a subgroup of patients who might be spared maintenance treatment, if the metabolic response after first-line chemotherapy could predict time-to-progression (TTP). Experimental Design: A total of 43 patients who underwent baseline FDG-PET scan and did not show disease progression (DP) after 4 cycles of first-line chemotherapy were enrolled and underwent second FDG-PET 3 weeks after completion of the first-line chemotherapy. The primary endpoint was to compare percent decrease in maximum standard uptake value (SUVmax) between early (TTP after second PET examination <8 weeks) and late (TTP ≥8 weeks) DP subgroups. Secondary endpoints were to determine whether fractional decrease in SUVmax could predict TTP and overall survival (OS), both calculated from the date of the second FDG-PET. Results: Percent decreases in SUVmax in late DP subgroup were greater than those in early DP subgroup (mean reduction, 54.7% ± 27.2% vs. 27.8% ± 46.8%, P = 0.021). Receiver operating characteristic curves identified a 50.0% decrease in SUVmax as the optimal threshold to distinguish these subgroups. Using this value as the cutoff resulted in a positive predictive value of 82.6% and negative predictive value of 60.0% in predicting TTP ≥8 weeks. Patients with SUVmax decrease <50% had significantly longer median TTP (3.0 vs. 1.5 months, P = 0.001) and OS (not reached vs. 14.2 months, P = 0.003). Conclusions: Fractional decrease in SUVmax of the main lesion after completion of 4 cycles of chemotherapy may discriminate patients with TTP ≥8 weeks and predict TTP and OS in patients with advanced NSCLC. Clin Cancer Res; 17(15); 5093–100. ©2011 AACR.