Clinical efficacy of Sep-Pak® assisted one pot automated synthesis of pharmaceutical grade [18F]FLT using 5′-O-(benzoyl)-2,3′-anhydrothymidine precursor

Automated radiochemical synthesis of pharmaceutical grade [18F]FLT using 3‐N‐Boc‐5′‐O‐dimethoxytrityl‐3′‐O‐nosyl‐thymidine precursor and its Sep‐Pak® purification employing selective elution from reversed phase

“…UV active HPLC chromatogram (Figure 3B) at 254 nm did not exhibited any peak. Thus, can be concluded [ 19 F]FLT formation in the final product could be below the detection limit of UV‐HPLC, as the limit of quantification (LOQ) and UV detection for semi‐preparative and analytical HPLC could be lower than the range of permissible chemical impurities ([ 19 F]FLT < 0.61 μg/ml) formed in the final product 2,19 …”

“…Thus, can be concluded [ 19 F]FLT formation in the final product could be below the detection limit of UV-HPLC, as the limit of quantification (LOQ) and UV detection for semipreparative and analytical HPLC could be lower than the range of permissible chemical impurities ([ 19 F] FLT < 0.61 μg/ml) formed in the final product. 2,19 In this respect, the UV/VIS spectral data were utilized to estimate the amount of [ 19 F]FLT coproduced with the [ 18 F]FLT. The standard curve revealed that the concentration of [ 19 F]FLT in the product thus produced were 0.36 ± 0.01 μg/ml (254 nm, Figure 4), which is much below the permissible limit of 0.61 μg/ml.…”

“…During the deprotection process, a very significant radiochemical impurity was generated, that is, the nucleoside isomers of [ 18 F]FLT, which is more lipophilic than [ 18 F]FLT [2]. Before introducing a washing step of SPE purification cartridges (light Alumina-N !…”

“…Earlier, the preparation of [ 18 F]FLT was facilitated using 5′‐O‐(4,4′‐dimethoxytriphenylmethyl)‐2,3′anhydrothymidine (DMTr‐Anhydro) and 5′‐O‐(Benzoyl)‐2,3′anhydrothymidine (Benzoyl‐Anhydro) 1,2 . However, the decay corrected RCY 14.3% and 5.67% of [ 18 F]FLT, using DMTr‐Anhydro and Benzoyl‐Anhydro, respectively, was improved by using a newly developed precursor, namely, 3‐N‐(2,4‐dimethoxybenzyl)‐1‐[5‐O‐(4,4′‐dimethoxytrityl)‐3‐O‐nosyl‐2‐deoxy‐β‐D‐lyxofuranosyl]thymine (DMB‐Nosyl), with 4‐nitrobenzene sulfonyl group as the leaving group 3 .…”

“…Earlier, the preparation of [ 18 F]FLT was facilitated using 5 0 -O-(4,4 0 -dimethoxytriphenylmethyl)-2,3 0 anhydrothymidine (DMTr-Anhydro) and 5 0 -O-(Benzoyl)-2,3 0 anhydrothymidine (Benzoyl-Anhydro). 1,2 However, the decay corrected RCY 14.3% and 5.67% of [ 18 F] FLT, using DMTr-Anhydro and Benzoyl-Anhydro, respectively, was improved by using a newly developed precursor, namely, 3-N-(2,4-dimethoxybenzyl)-1-[5-O-(4,4 0 -dimethoxytrityl)-3-O-nosyl-2-deoxy-β-Dlyxofuranosyl]thymine (DMB-Nosyl), with 4-nitrobenzene sulfonyl group as the leaving group. 3 A RCY of 7% [ 18 F]FLT was obtained while using the DMB-Nosyl precursor, since this precursor has the heterocyclic sulfonyl moiety as the leaving group which is highly susceptible for displacement by a nucleophile ( 18 F À ), in presence of a polar aprotic solvent.…”