Rationale of 5-125I-Iodo-4′-Thio-2′-Deoxyuridine as a Potential Iodinated Proliferation Marker

Journal of Nuclear Medicine

Akio Hayashi¹  Mikiko Sato¹  Yuichi Yoshimura¹  Yasuhisa Fujibayashi¹  Hiromichi Tanaka¹  Kazuhiro Haraguchi¹  Jun Toyohara¹  Yoshiharu Yonekura¹ 

关键词: 5-¹²⁵I-iodo-4′-thio-2′-deoxyuridine;    5-¹²⁵I-iodo-1-(4-thio-β-d-arabinofuranosyl)uracil;    5-¹²⁵I-iodo-2′-deoxyuridine;    nucleoside kinases;    thymidine phosphorylase;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown