Synthesis and biodistribution of 3′-fluoro-5-[¹³¹I]iodo-2′-deoxyuridine: a comparative study of [¹³¹I]FLIdU and [¹⁸F]FLT

Abstract 

The radioiodinated 3′-fluorothymidine (FLT) analogue 3′-fluoro-5-[¹³¹I]iodo-2′-deoxyuridine ([¹³¹I]FLIdU) was synthesized, with iodine mimicking the methyl group of pyrimidine. [¹³¹I]FLIdU was accessible by direct electrophilic iodination using Iodogen as oxidant. Optimized amounts of the oxidant allowed radiochemical yields of about 70% after a reaction time of 10 min in an aqueous buffer medium at 90°C. The uptake of [¹³¹I]FLIdU in a DoHH2 leukemia xenograft mouse model and in healthy mice revealed moderate FLIdU accumulation, followed by a significant washout of activity in proliferating tissues such as splenic and tumor tissues. In contrast, intraperitoneal coinjection with [¹⁸F]FLT showed high uptake and high activity retention up to 2 h, in both splenic and tumor tissues. Uptake in stomach tissues and increasing fractions of [¹³¹I]iodide in urine indicated metabolic instability of [¹³¹I]FLIdU due to rapid deiodination. Therefore, [¹³¹I]FLIdU alone does not seem to be a promising compound, neither for diagnostic imaging nor for potential therapeutic applications.

Keywords: Pyrimidine nucleosides, Radioiodine labeling, [¹³¹I]FLIdU, Pharmacokinetics, Biodistribution in SCID mice, DoHH2 xenograft model