Search Results
Abstract
[18F]FLT (3
-deoxy-3-[18F]fluorothymidine) turned out to be a tracer particularly suitable for PET imaging of tumor proliferation because of lacking degradation in vivo. To facilitate clinical studies with [18F]FLT, we investigated two new easily accessible precursors, 2,3-anhydrothymidine (AThy) and 5-O-(4,4-dimethoxytriphenylmethyl)-2,3-anhydrothymidine (DMTThy), using a common approach for introducing the label with nucleophilic [18F]fluoride. Radiochemical yields were determined in dependence on substrate concentration, reaction time and temperature. In the case of AThy (10 mg), best FLT yields were 5.3%±1.2 (130 °C, 30 min). Labeling of DMTThy (10 mg) gave 14.3%±3.3 at 160 °C within 10 minutes. Starting with an aqueous solution of 20 GBq [18F]fluoride the new method allows to produce 1.3 GBq [18F]FLT within 90 minutes ready for intravenous injection. The new labeling procedures allow [18F]FLT synthesis without lengthy preparation of the precursor and with high reproducibility mandatory for clinical application.
Abstract
The study is aimed at the analysis and identification of radiochemical and chemical impurities present in [18F]FLT synthesized by a simplified combination-column purification procedure, instead of the currently used HPLC purification. HPLC analysis of the final product showed an anionic radioactive byproduct, which was established as [18F]4-FBSA. The identity of the product was also confirmed by the radiofluorination of nosyl chloride. Mass spectrum analysis of both a decayed sample of [18F]FLT and fluorinated nosyl chloride showed a major peak at 242. We have also investigated the possible interference of this byproduct during PET-imaging in rabbits.
Abstract
For in vivo measurement of DNA synthesis in the patient"s tumour 3"-[18F]fluoro-3"-deoxythymidine (FLT) has been shown to be very promising. As a new labeling precursor 5"-O-(4,4"-dimethoxytrityl)-2,3"-anhydrothymidine (DMTThy) was chosen and an organic synthesis was developed including NMR and MS data for characterisation. The 18F-labeling of DMTThy can be performed within 30 minutes in radiochemical yields of almost 20% when using polar solvents such as DMF or DMSO and a temperature of 160 °C. Hydrolysis is completed with 1N HCl at 50 °C within 10 minutes without losses.
Abstract
[18F]-3′-deoxy-3′-fluorothymidine ([18F]FLT) is an established positron emission tomograph (PET)—radiopharmaceutical to study cell-proliferation rate in tumors. Very low practical yield, uncertain and time-consuming high performance liquid chromatography (HPLC) purification, are the main obstacles for the routine use of [18F]FLT in clinical PET. To obviate these difficulties, we have developed a fully automated radiosynthesis procedure for [18F]FLT using 5′-O-(4,4′-dimethoxytriphenylmethyl)-2,3′-anhydro-thymidine (DMTThy) and simplified single neutral alumina column purification. The [18F]FLT yield was 8.48 ± 0.93% (n = 5) (without radioactive decay correction) in a synthesis time of 68 ± 3 min. The radiochemical purity was greater than 95% as confirmed by analytical HPLC using reference standard FLT and also free of non-radioactive impurity. Soluble aluminum in the final product was much below the permissible limits. Di-methyl sulfoxide (DMSO), the reaction medium, could be detected in the final product in trace amounts, well below the permissible levels. The synthesized [18F]FLT was sterile and bacterial endotoxin free by appropriate tests. PET imaging study in normal rabbits showed distinct localization of [18F]FLT in organs having rapid cell division rate like bone marrow, guts and snout and the excretion was through the renal route. There were no significant uptakes in bone and brain. The former finding confirms the in vivo stability of the [18F]FLT. This simplified radiosynthesis procedure can easily be adapted in any commercial or indigenous [18F]FDG synthesis module for routine [18F]FLT synthesis without the need of additional automation for HPLC purification.
