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

Pharmaceutical grade 3'-deoxy-3'-[F-18]fluorothymidine [F-18]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 [F-18]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 mu mole) 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 simplified method for solid-phase purification of [F-18]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 similar to 3.8 at 90 min. PET/CT imaging of normal rabbit injected with [F-18]FLT shows selective uptake in the bone marrow and small intestine. [F-18]FLT was found to be excreted through the kidneys and get collected in the urinary bladder, 120 min post injection. PET/CT imaging performed in rabbit model at 30, 60, 90, and 120 min post [F-18]FLT injections showed concordance with tissue distribution kinetics of mice tumor model.