Radioiodination and biological evaluation of Cladribine as potential agent for tumor imaging and therapy

Abstract

Cladribine, a purine analogue antimetabolite, was radioiodinated with 125I via direct electrophilic substitution reaction. The maximum radiochemical yield (92.5 ± 0.8%) was obtained when the reaction was done at ambient temperature for 30 min using 100 μg of Cladribine and 10 μg N-chlorosuccinamide (NCS) in 150 μL of 0.2 M phosphate buffer, pH 7. In vitro stability studies of HPLC purified 125I-Cladribine sample dissolved in 0.5 ml of 0.2 M phosphate buffer pH 7 at ambient temperature showed that 125I-Cladribine is stable up to 12 h post labeling. Biodistribution results revealed excretion of 125I-Cladribine mainly by kidneys. The uptake of 125I-Cladribine in the induced Ehrlich Ascites Carcinoma was 2.8 ± 0.4 %ID/g at 1 h post injection with maximum tumor/muscle ratio of 5.5. The good uptake of 125I-Cladribine confirms the molecular docking studies results which indicate that iodinated Cladribine binds with polymerase enzyme with a good -CDOCKER energy. As a result, radioiodinated Cladribine may be used as a valuable agent for tumor diagnosis and therapy.