Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. (18)F-methyl-choline ((18)F-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 (18)F-ethyl-tyrosine ((18)F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. (18)F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate (18)F-FCH and (18)F-FET uptake by human glioblastoma T98G cells.
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Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 10(5) 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 (18)F-FCH and (18)F-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 × 10(5) 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.
A significant uptake of (18)F-FCH was seen in T98G cells at 60, 90 and 120 minutes. The percentage uptake of (18)F-FET in comparison to (18)F-FCH was lower by a factor of more than 3, with different kinetic curves.(18)F-FET showed a more rapid initial uptake up to 40 minutes and (18)F-FCH showed a progressive rise reaching a maximum after 90 minutes.
(18)F-FCH and (18)F-FET are candidates for neuro-oncological PET imaging. (18)F-FET could be the most useful oncological PET marker in the presence of reparative changes after therapy, where the higher affinity of (18)F-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.
Radiology and oncology. 2016 Apr 19*** epublish ***
Marco Giovanni Persico, Federica Eleonora Buroni, Francesca Pasi, Lorenzo Lodola, Carlo Aprile, Rosanna Nano, Marina Hodolic
Department of Oncohaematology, Nuclear Medicine Unit, IRCCS San Matteo Hospital Foundation, Pavia, Italy., Department of Oncohaematology, Nuclear Medicine Unit, IRCCS San Matteo Hospital Foundation, Pavia, Italy., Department of Oncohaematology, Radiotherapy Unit, IRCCS San Matteo Hospital Foundation, Pavia, Italy., Department of Oncohaematology, Nuclear Medicine Unit, IRCCS San Matteo Hospital Foundation, Pavia, Italy., Department of Oncohaematology, Nuclear Medicine Unit, IRCCS San Matteo Hospital Foundation, Pavia, Italy., Department of Biology and Biotecnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy., Nuclear medicine research department, Iason, Graz, Austria.