Imaging of proliferation in hepatocellular carcinoma with the in vivo marker18F-fluorothymidine

Abstract

We determined the ability of PET with the thymidine analog 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) to detect hepatocellular carcinoma (HCC). Methods: In this pilot study, 18F-FLT PET was performed in 18 untreated patients with clinically suspected HCC. Routine diagnostic procedures included ultrasound, MRI, or contrast-enhanced spiral CT of the upper gastrointestinal tract in all patients. At 45-60 min after the intravenous injection of approximately 270-340 MBq of 18F-FLT, emission and transmission scanning was performed with a high-resolution PET scanner. Tracer uptake in the tumor and surrounding liver tissue was evaluated semiquantitatively by calculation of mean and maximum standardized uptake values (SUVs). Results were correlated with those of the conventional imaging methods. Results: A total of 13 of 18 tumors (sensitivity, 72%; 95% confidence interval [CI], 47%-90%) showed focal 18F-FLT uptake higher than surrounding liver activity and were detectable as hot lesions. Five tumors were characterized as photopenic lesions or contained a mixture of hot and cold lesions exhibiting a comparable or lower 18F-FLT uptake than the surrounding liver tissue. When all lesions were considered, the mean 18F-FLT SUV was 7.8 (range, 2.5-11.1), and the maximum 18F-FLT SUV was 9.3 (range, 2.9-14.3). Histology and clinical follow-up revealed HCC in 16 patients and cholangiocarcinoma in 2 patients. In the subgroup of HCC, the sensitivity for tumor detection was 69% (11/16; 95% CI, 41%-89%). Correlation analysis demonstrated a significant positive relationship between the proliferation marker MIB-1 and the mean SUV (r = 0.66, P = 0.02). Survival analysis (Cox proportional hazards regression) for initial 18F-FLT uptake (mean and maximum SUVs) revealed increased hazard ratios (mean SUV, 1.20; maximum SUV, 1.12), but because of the small number of events, these results were not statistically significant. Conclusion: In this pilot study, HCC tumors showed a mixed uptake pattern for the in vivo proliferation marker 18F-FLT. A total of 69% of the HCC lesions showed 18F-FLT uptake higher than that of the surrounding liver tissue, whereas the remaining lesions were photopenic or contained a mixture of hot and cold lesions. High initial 18F-FLT uptake seems to be associated with reduced overall survival and could be an important prognostic factor if this tendency can be confirmed in a larger prospective trial. Copyright © 2009 by the Society of Nuclear Medicine, Inc.