Background: 3'-deoxy-3'-[F-18]fluorothymidine (F-18-FLT) has been used to evaluate tumor malignancy and cell proliferation in human brain gliomas. However, F-18-FLT has several limitations in clinical use. Recently, C-11-labeled thymidine analogue, 4'-[methyl-C-11]thiothymidine (C-11-4DST), became available as an in vivo cell proliferation positron emission tomography (PET) tracer. The present study was conducted to evaluate the usefulness of C-11-4DST PET in the diagnosis of human brain gliomas by comparing with the images of F-18-FLT PET.
Methods: Twenty patients with primary and recurrent brain gliomas underwent F-18-FLT and C-11-4DST PET scans. The uptake values in the tumors were evaluated using the maximum standardized uptake value (SUVmax), the tumor-to-normal tissue uptake (T/N) ratio, and the tumor-to-blood uptake (T/B) ratio. These values were compared among different glioma grades. Correlation between the Ki-67 labeling index and the uptake values of C-11-4DST and F-18-FLT in the tumor was evaluated using linear regression analysis. The relationship between the individual F-18-FLT and C-11-4DST uptake values in the tumors was also examined.
Results: C-11-4DST uptake was significantly higher than that of F-18-FLT in the normal brain. The uptake values of C-11-4DST in the tumor were similar to those of F-18-FLT resulting in better visualization with F-18-FLT. No significant differences in the uptake values of F-18-FLT and C-11-4DST were noted among different glioma grades. Linear regression analysis showed a significant correlation between the Ki-67 labeling index and the T/N ratio of C-11-4DST (r = 0.50, P < 0.05) and F-18-FLT (r = 0.50, P < 0.05). Significant correlations were also found between the Ki-67 labeling index and the T/B ratio of C-11-4DST (r = 0.52, P < 0.05) and F-18-FLT (r = 0.55, P < 0.05). A highly significant correlation was observed between the individual T/N ratio of C-11-4DST and F-18-FLT in the tumor (r = 0.79, P = 0.0001).
Conclusions: The present study demonstrates that C-11-4DST is useful for the imaging of human brain gliomas with PET. A relatively higher background uptake of C-11-4DST in the normal brain compared to F-18-FLT limits the detection of low-tracer-uptake tumors. Moreover, no superiority was found in C-11-4DST over F-18-FLT in the evaluation of cell proliferation.