18F-FET and 18F-FCH uptake in human glioblastoma T98G cell lines

Abstract

Abstract Background Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. 18F-methyl-choline (18F-FCH) is frequently used in staging and detection of recurrent prostate cancer disease as well as some brain tumours; however accumulation in inflammatory tissue limits its specificity. The 18F-ethyl-tyrosine (18F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. 18F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate 18F-FCH and 18F-FET uptake by human glioblastoma T98G cells. Material and methods Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 105 cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO2 in complete medium. Equimolar amounts of radiopharmaceuticals were added to cells for different incubation times (20 to 120 minutes) for 18F-FCH and 18F-FET respectively. The cellular radiotracer uptake was determined with a gamma counter. All experiments were carried out in duplicate and repeated three times. The uptake measurements are expressed as the percentage of the administered dose of tracer per 2 × 105 cells. Data (expressed as mean values of % uptake of radiopharmaceuticals) were compared using parametric or non-parametric tests as appropriate. Differences were regarded as statistically significant when p<0.05. Results A significant uptake of 18F-FCH was seen in T98G cells at 60, 90 and 120 minutes. The percentage uptake of 18F-FET in comparison to 18F-FCH was lower by a factor of more than 3, with different kinetic curves.18F-FET showed a more rapid initial uptake up to 40 minutes and 18F-FCH showed a progressive rise reaching a maximum after 90 minutes. Conclusions 18F-FCH and 18F-FET are candidates for neuro-oncological PET imaging. 18F-FET could be the most useful oncological PET marker in the presence of reparative changes after therapy, where the higher affinity of 18F-FCH to inflammatory cells makes it more difficult to discriminate between tumour persistence and non-neoplastic changes. Additional studies on the influence of inflammatory tissue and radionecrotic cellular components on radiopharmaceutical uptake are necessary.