Synthesis and biodistribution of 3'-fluoro-5-[(131)I]iodo-2'-deoxyuridine: a comparative study of [(131)I]FLIdU and [(18)F]FLT.
The radioiodinated 3'-fluorothymidine (FLT) analogue 3'-fluoro-5-[(131)I]iodo-2'-deoxyuridine ([(131)I]FLIdU) was synthesized, with iodine mimicking the methyl group of pyrimidine. [(131)I]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 degrees C. The uptake of [(131)I]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 [(18)F]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 [(131)I]iodide in urine indicated metabolic instability of [(131)I]FLIdU due to rapid deiodination. Therefore, [(131)I]FLIdU alone does not seem to be a promising compound, neither for diagnostic imaging nor for potential therapeutic applications.
Vogg
Andreas T J
AT
Clinic for Nuclear Medicine, D-89081 Ulm, Germany. andreas.vogg@itm.ag
Buck
Andreas K
AK
Schmid
Michaela
M
Neumaier
Bernd
B
Wczasek
Katrin
K
Zlatopolskiy
Boris D
BD
Reske
Sven N
SN
D000818:Animals; D045744:Cell Line, Tumor; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D015224:Dideoxynucleosides / Q000737:chemistry / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008223:Lymphoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D016513:Mice, SCID; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
C521345:3'-fluoro-5-iodo-2'-deoxyuridine; D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine; D003857:Deoxyuridine