Comparison of 4′-[methyl-11C]thiothymidine (11C-4DST) and 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) PET/CT in human brain glioma imaging

Abstract

Background3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) has been used to evaluate tumor malignancy and cell proliferation in human brain gliomas. However, 18F-FLT has several limitations in clinical use. Recently, 11C-labeled thymidine analogue, 4′-[methyl-11C]thiothymidine (11C-4DST), became available as an in vivo cell proliferation positron emission tomography (PET) tracer. The present study was conducted to evaluate the usefulness of 11C-4DST PET in the diagnosis of human brain gliomas by comparing with the images of 18F-FLT PET.MethodsTwenty patients with primary and recurrent brain gliomas underwent 18F-FLT and 11C-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 11C-4DST and 18F-FLT in the tumor was evaluated using linear regression analysis. The relationship between the individual 18F-FLT and 11C-4DST uptake values in the tumors was also examined.Results11C-4DST uptake was significantly higher than that of 18F-FLT in the normal brain. The uptake values of 11C-4DST in the tumor were similar to those of 18F-FLT resulting in better visualization with 18F-FLT. No significant differences in the uptake values of 18F-FLT and 11C-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 11C-4DST (r = 0.50, P < 0.05) and 18F-FLT (r = 0.50, P < 0.05). Significant correlations were also found between the Ki-67 labeling index and the T/B ratio of 11C-4DST (r = 0.52, P < 0.05) and 18F-FLT (r = 0.55, P < 0.05). A highly significant correlation was observed between the individual T/N ratio of 11C-4DST and 18F-FLT in the tumor (r = 0.79, P = 0.0001).ConclusionsThe present study demonstrates that 11C-4DST is useful for the imaging of human brain gliomas with PET. A relatively higher background uptake of 11C-4DST in the normal brain compared to 18F-FLT limits the detection of low-tracer-uptake tumors. Moreover, no superiority was found in 11C-4DST over 18F-FLT in the evaluation of cell proliferation.

Correlation of 4′-[methyl-11C]-Thiothymidine Uptake with Ki-67 Immunohistochemistry in Patients with Newly Diagnosed and Recurrent Gliomas

“…Toyota et al evaluated 4DST uptake and proliferative activity in 20 patients with gliomas, including 11 recurrent gliomas [10]. They showed a weak correlation between 4DST T/N ratio and Ki-67 index [10]. The present study also showed a weak correlation between 4DST T/N ratio and Ki-67 index in newly diagnosed gliomas.…”

“…In a previous study, an initial clinical trial in only 6 patients with brain tumor was indicated that 4DST PET was feasible for imaging brain tumors [9]. Toyota et al evaluated 4DST uptake and proliferative activity in 20 patients with gliomas, including 11 recurrent gliomas [10]. They showed a weak correlation between 4DST T/N ratio and Ki-67 index [10].…”

“…A 11 C-4DST PET pilot study of 6 patients with various brain tumors showed that 11 C-4DST PET is feasible for brain tumor imaging and can be performed with acceptable dosimetry and pharmacologic safety at a suitable dose for adequate imaging [9]. In a mixed population of patients with newly diagnosed and recurrent gliomas, Toyota et al has recently demonstrated that 4DST PET is feasible for evaluating cell proliferation [10]. These results indicate that 4DST has great potential for imaging cell proliferation.…”

Brain Tumor Imaging

“…Ultimately, imaging will only be used widely and routinely if it addresses an unmet clinical need that cannot be satisfied by competing technologies. In this respect, the capability of imaging is unique when used to guide surgery or 68 Mittra et al, 69 Bruehlmeier et al, 70 Kondo et al, 71 Yamamoto et al, 72 Toyota et al, 73…”

Repeatability of 18F-FLT PET in a Multicenter Study of Patients with High-Grade Glioma

“…Sustained retention of 18 F-FLT in tumors long after gadolinium-based contrast agents have washed out suggests an additional trapping process. Several papers (6,(9)(10)(11)(12) report a correlation between 18 F-FLT uptake in brain tumors, measured using SUV, and the histopathologic proliferation marker Ki-67. The correlation is usually quite weak, consistent with the thought that 18 F-FLT uptake is driven not just by proliferation but by additional mechanisms, such as BBB permeability and tumor blood flow.…”