BARC/PUB/2022/1016

 
 

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

 
     
 
Author(s)

Mitra, A.; Chakraborty, A.; Upadhye, T.; Tawate, M.; Lad, S.; Sahu, S.; Rajesh, C.; Bagul, S.; Pawar, Y.; Ray, M. K.; and others
(RMC)

Source

Journal of Labelled Compounds and Radiopharmaceuticals, 2022. Vol. 65: pp. 206-222

ABSTRACT

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 simplified 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 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 [18F]FLT injections showed concordance with tissue distribution kinetics of mice tumor model.

 
 
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