RT Journal Article SR Electronic T1 Rationale of 5-125I-Iodo-4′-Thio-2′-Deoxyuridine as a Potential Iodinated Proliferation Marker JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1218 OP 1226 VO 43 IS 9 A1 Toyohara, Jun A1 Hayashi, Akio A1 Sato, Mikiko A1 Tanaka, Hiromichi A1 Haraguchi, Kazuhiro A1 Yoshimura, Yuichi A1 Yonekura, Yoshiharu A1 Fujibayashi, Yasuhisa YR 2002 UL http://jnm.snmjournals.org/content/43/9/1218.abstract AB The aim of this investigation was to synthesize and test a novel metabolically stable iodinated nucleoside as a proliferation-imaging agent for SPECT. Methods: 5-Iodo-4′-thio-2′-deoxyuridine (ITdU) and 5-iodo-1-(4-thio-β-d-arabinofuranosyl)uracil (ITAU) were tested. The radiolabeling of ITdU and ITAU with 125I was achieved by a destannylation reaction of the trimethylstannyl precursor of each nucleoside. The products were isolated in high yields and with >99% radiochemical purities. Results: 125I-ITdU was effectively phosphorylated by cytosolic nucleoside kinases and specifically incorporated into a thymidine kinase-expressing L-M cell rather than a thymidine kinase-deficient mutant L-M (TK−) cell. In addition, an in vitro cell metabolism study of 125I-ITdU clarified that 125I-ITdU was effectively and specifically incorporated into a DNA fraction (>90% at 60 min). Therefore, 125I-ITdU was proven to be an ideal DNA synthesis marker such as 5-125I-iodo-2′-deoxyuridine (IUdR). In contrast, 125I-ITAU was neither remarkably phosphorylated by cytosolic nucleoside kinases nor notably incorporated into an L-M cell rather than an L-M (TK−) cell. 125I-ITdU and 125I-ITAU showed a higher resistance to phosphorolytic cleavage by recombinant thymidine phosphorylase than did 125I-IUdR. Furthermore, biodistribution of 125I-ITdU and 125I-ITAU revealed better in vivo stability of radioiodination than that of 125I-IUdR. 125I-ITdU also displayed a significantly higher uptake in proliferating organs (thymus, spleen, small intestine, and bone) than in nonproliferating organs (brain, muscle, liver, and lung), as did 125I-IUdR, at 18 h after injection. As indicated by the in vitro study, 125I-ITAU did not show any significant uptake in proliferating organs. Conclusion: Radioiodine-labeled ITdU is potentially useful as a proliferation-imaging agent, and further studies should clarify the usefulness of this compound as a tumor-imaging agent.