Correlation of 4'-[methyl- super(11)C]-thiothymidine uptake with Ki-67 immunohistochemistry and tumor grade in patients with newly diagnosed gliomas in comparison with super(11)C-methionine uptake

A novel radiopharmaceutical, 4'-[methyl- super(11)C]thiothymidine ( super(11)C-4DST), has been developed as an in vivo cell proliferation marker based on the DNA incorporation method. The purpose of this study was to evaluate super(11)C-4DST uptake in patients with newly diagnosed glioma and to correlate the results with proliferative activity and tumor grade, in comparison with l-[methyl- super(11)C]-methionine ( super(11)C-MET). Investigations of super(11)C-4DST and super(11)C-MET PET/CT were performed retrospectively in 23 patients with newly diagnosed glioma. The maximum standardized uptake value (SUVmax) for tumor (T) and the mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) was defined as the volume with a threshold of 40 % of the SUVmax. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Of 23 gliomas examined, super(11)C-4DST PET/CT and super(11)C-MET PET/CT detected 20 and 22, respectively. Linear regression analysis between super(11)C-4DST and super(11)C-MET indicated a weak correlation for SUVmax (r = 0.54, P < 0.008), for T/N ratio (r = 0.56, P < 0.006), and for MTV (r = 0.60, P < 0.003). Linear regression analysis indicated a weak correlation between super(11)C-4DST and Ki-67 index for SUVmax (r = 0.46, P < 0.03), for T/N ratio (r = 0.43, P < 0.05), and for MTV (r = 0.68, P < 0.001) and between super(11)C-MET MTV and Ki-67 index (r = 0.43, P < 0.04). Using super(11)C-4DST, there was a significant difference in SUVmax between grades II and IV (P < 0.03) and in MTV between grades II and IV (P < 0.009) and grades III and IV (P < 0.02). Using super(11)C-MET, there was a significant difference in SUVmax (P < 0.009) and T/N ratio (P < 0.02) between grades II and IV and in MTV between grades II and IV (P < 0.03) and grades III and IV (P < 0.02). super(11)C-4DST PET/CT is feasible for imaging of brain gliomas, as well as super(11)C-MET PET/CT. Especially, it showed the highest correlation coefficient between super(11)C-4DST MTV and Ki-67 index in newly diagnosed gliomas.