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

Shown are the modification in TRACERlab FX radiochemistry module and the automated one-pot radiochemical synthesis of18FLT by selective elution from HLB Sep-Pak. Specifications of produced18FLT are in accordance with Investigational New Drug Program by National Cancer Institute-Cancer Imaging Program. Pharmaceutical grade 3 ′-deoxy-3′-[18F]fluorothymidine [18F]FLT was synthesized using 3-N-Boc-5 ′-O-dimethoxytrityl-3′-O-nosyl-thymidine (BOC-Nosyl) precursor, in the general purpose TRACERlab FX modules. Purification of [18F]FLT, via solid phase extraction (SPE) after radiosynthesis, using a combination of different SPE cartridges, yielded satisfactory results, with radiochemical and chemical purity>99%. While the non-decay corrected radiochemical yield (RCY) with 20  mg (24 μmole) of BOC-Nosyl precursor was found to be 6.80 ± 0.16%, the decay corrected radiochemical yield (RCY) was 9.95 ± 0.24%. Residual acetone, acetonitrile, and ethanol levels were found to be 22.97 ± 0.76, 109.08 ± 0.93, and 7,666.45 ± 3.7 ppm, respectively. A simplif ied method for solid-phase purification of [18F]FLT was developed, circumventing the need for HPLC purification. Biodistribution in C57BL/6 mice with B16F10 cell line-induced melanoma showed tumor to blood ratio of ~3.8 at 90  min. PET/CT imaging of normal rabbit injected with [18F]FLT shows selective uptake in the bone marrow and small intestine. [18F]FLT was found to be excreted through the kidneys and ge...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research