[en] 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^oC. 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

[en] Several radiolabeled thymidine analogs as metabolic probes of cell proliferation were developed specifically addressing DNA synthesis. Thymidine analogs containing carboranylalkyl groups for neutron capture therapy at the N-3 position were found to be good substrates for cytosolic thymidine kinase 1 (TK1). According to this approach, a DO3A macrocycle in N-3 position was attached to thymidine. The 3-DO3A thymidine analog was labeled with ⁶⁸Ga and ¹¹¹In. Different lipophilicities of the corresponding radiometal-thymidines were detected via RP-HPLC. [¹¹¹In]DO3A-thymidine ([¹¹¹In]D3T) was evaluated for cellular uptake in different cell lines (HL60 and DoHH2). Cellular uptake was low in both cell lines. Phosphorylation of the radioconjugates by TK1 was negligible. Although stable complexation of radiometals to thymidine was obtained, introduction of the macrocycle DO3A reduced the affinity to cytosolic TK1 drastically. Low cellular uptake can be ascribed to missing substrate specificity of [¹¹¹In]DO3A-thymidine for TK1. The absence of substrate specificity may be due to the bulky macrocyclic chelator and partial charges remaining on the coordination sphere due to a more complex solution structure