title: Imaging of proliferation in hepatocellular carcinoma with the in vivo marker 18F-fluorothymidine.
abstract: We determined the ability of PET with the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) to detect hepatocellular carcinoma (HCC).
  
  
  METHODS
  In this pilot study, (18)F-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 (18)F-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 (18)F-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 (18)F-FLT uptake than the surrounding liver tissue. When all lesions were considered, the mean (18)F-FLT SUV was 7.8 (range, 2.5-11.1), and the maximum (18)F-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 (18)F-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.
  
  
  CONCLUSIONS
  In this pilot study, HCC tumors showed a mixed uptake pattern for the in vivo proliferation marker (18)F-FLT. A total of 69% of the HCC lesions showed (18)F-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 (18)F-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.
authors.affiliation: Department of Internal Medicine II, Technische Universität München, Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Eckel
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Schmidt
authors.forename: Claudia
authors.initials: C
authors.lastname: Hillerer
authors.forename: Hinrich A
authors.initials: HA
authors.lastname: Wieder
authors.forename: Bernd-Joachim
authors.initials: BJ
authors.lastname: Krause
authors.forename: Tibor
authors.initials: T
authors.lastname: Schuster
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Buck
mesh_terms: D000368:Aged; D000465:Algorithms; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging*; D015224:Dideoxynucleosides; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine