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

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 7666.45 ± 3.7 ppm respectively. A simplified method for solid-phase p urification 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 minutes. 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 get collected in the urinary bladder, 120 minutes post injection. PET/CT imaging performed in rabbit model at 30, 60, 90 and 120 minutes post [18F]FLT injections, showed concordance with tissue distribution kinetics of mice tumor model.
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research