3′-Deoxy-3′-[18F]-fluorothymidine ([18F]-FLT) transport in newly diagnosed glioma: correlation with nucleoside transporter expression, vascularization, and blood–brain barrier permeability

Abstract

3'-Deoxy-3'-[(18)F]-fluorothymidine ([(18)F]-FLT), a marker of cellular proliferation, has been used in positron emission tomography (PET) examination of gliomas. The aim of this study was to investigate whether the uptake of [(18)F]-FLT in glioma correlates with messenger RNA (mRNA) levels of the equilibrative nucleoside transporter 1 (ENT1), microvascular density (assessed by CD34 immunohistochemistry), and the blood-brain barrier (BBB) breakdown. A total of 21 patients with newly diagnosed glioma were examined with [(18)F]-FLT PET. Tumor lesions were identified as areas of focally increased [(18)F]-FLT uptake, exceeding that of surrounding normal tissue. Dynamic analysis of [(18)F]-FLT PET revealed correlations between the phosphorylation rate constant k 3 and ENT1 expression; however there was no correlation between the kinetic parameters and CD34 score. There was a good correlation between the gadolinium (Gd) enhancement score (evaluating BBB breakdown) and ENT1 expression, CD34 score, and Ki-67 index. This preliminary study suggests that ENT1 expression might not reflect accumulation of [(18)F]-FLT in vivo due to BBB permeability in glioma.