OtherBasic Science Investigations

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

Jun Toyohara, Akio Hayashi, Mikiko Sato, Hiromichi Tanaka, Kazuhiro Haraguchi, Yuichi Yoshimura, Yoshiharu Yonekura and Yasuhisa Fujibayashi
Journal of Nuclear Medicine September 2002, 43 (9) 1218-1226;

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Synthetic pathway for preparation of radiolabeled ITdU and ITAU by destannylation.

  • FIGURE 2.
    FIGURE 2.

    Time-dependent incorporation of radioactivity into Lewis lung carcinoma cells. (A) Radioactivity of acid-soluble small molecule, DNA, RNA, and protein fractions is shown. (B) Time-dependent percentage of radioactivity distribution in each fraction of Lewis lung carcinoma. Data are expressed as mean ± SD for 3 experiments.

  • FIGURE 3.
    FIGURE 3.

    Uptake of iodonucleosides, expressed as organ-to-blood ratio of radioactivity. Animals were killed at 18 h after injection. Data are expressed as mean ± SD for 3 experiments. Iodonucleosides showed higher uptake in proliferation organs (femur, spleen, intestine, and thymus) than in nonproliferating organs (muscle, liver, and lung). Statistical significance between 125I-IUdR uptake and 125I-ITdU uptake was observed in intestine and thymus (P < 0.05; Student t test).

Tables

  • TABLE 1

    Relative Phosphorylation of Iodonucleosides by Nucleoside Kinases

    Nucleosidepmol phosphorylated*Relative potency
    IUdR1,620.8 ± 123.41.00
    ITdU802.4 ± 67.90.50
    ITAU13.3 ± 0.6<0.01

    • ↵* pmol phosphorylated = pmol/mg protein/h.

  • TABLE 2

    Susceptibility of Iodonucleosides to Glycosidic Bond Cleavage

    Nucleosidepmol IU formed*Relative IU formation
    IUdR138,606.2 ± 14,902.31.00
    ITdU3,778.7 ± 692.00.03
    ITAU514.8 ± 367.0<0.01

    • ↵* pmol IU formed = pmol/unit/30 min.

  • TABLE 3

    Cell Uptake by LL/2, L-M, and L-M (TK−) Cell Lines

    NucleosideTracer uptake* (relative uptake ratio)
    LL/2L-ML-M (TK−)
    IUdR539.7 ± 81.777.8 ± 7.4†27.9 ± 2.9
    (6.9)(2.8)
    ITdU226.7 ± 13.110.9 ± 1.5†3.9 ± 0.6
    (20.8)(2.8)
    ITAU1.1 ± 0.01.7 ± 0.3‡1.2 ± 0.2
    (0.6)(1.4)

    • ↵* Tracer uptake = pmol/mg protein/h.

    • ↵† P < 0.0005 compared with L-M (TK−).

    • ↵‡ P < 0.05 compared with L-M (TK−) (Student t test).

    • Data in parentheses in LL/2 row and L-M row indicate relative uptake ratios of LL/2 compared with those of L-M cells and relative uptake ratios of L-M compared with those of L-M (TK−), respectively.

  • TABLE 4

    Biodistribution of 125I-IUdR in Normal Mice (n = 3)

    Organ1 h1.5 h2 h8 h18 h
    Blood7.6 ± 0.85.4 ± 1.25.3 ± 0.51.1 ± 0.10.8 ± 1.1
    Spleen4.7 ± 0.64.6 ± 1.24.7 ± 2.23.1 ± 1.51.7 ± 0.9
    Intestine5.0 ± 0.23.3 ± 0.74.5 ± 0.52.4 ± 0.21.4 ± 0.4
    Thymus6.6 ± 1.14.4 ± 1.64.3 ± 1.01.8 ± 0.31.8 ± 1.5
    Femur4.5 ± 0.53.6 ± 0.83.7 ± 0.51.6 ± 0.11.1 ± 0.4
    Thyroid113.0 ± 30.880.7 ± 51.9112.1 ± 22.332.9 ± 13.59.7 ± 8.0
    Lung5.1 ± 0.43.6 ± 0.83.6 ± 0.30.9 ± 0.40.6 ± 0.7
    Heart2.8 ± 0.52.1 ± 0.51.9 ± 0.10.4 ± 0.00.3 ± 0.3
    Muscle1.4 ± 0.21.5 ± 0.31.4 ± 0.50.3 ± 0.10.1 ± 0.2
    Liver2.7 ± 0.42.1 ± 0.51.9 ± 0.20.4 ± 0.10.3 ± 0.3
    Brain0.3 ± 0.00.2 ± 0.10.2 ± 0.00.0 ± 0.00.0 ± 0.0
    Kidney5.9 ± 0.44.8 ± 1.53.4 ± 0.30.7 ± 0.10.6 ± 0.8

    • Data are expressed as percentage injected dose per gram (mean ± SD).

  • TABLE 5

    Biodistribution of 125I-ITdU in Normal Mice (n = 3)

    Organ1 h1.5 h2 h8 h18 h
    Blood2.5 ± 0.32.6 ± 0.61.6 ± 0.70.7 ± 0.20.1 ± 0.0
    Spleen1.1 ± 0.11.7 ± 0.31.1 ± 0.30.5 ± 0.10.3 ± 0.0
    Intestine1.9 ± 0.11.9 ± 0.51.7 ± 0.41.7 ± 0.50.9 ± 0.1
    Thymus1.8 ± 0.11.8 ± 0.41.4 ± 0.72.2 ± 1.31.1 ± 0.4
    Femur1.0 ± 0.11.0 ± 0.20.9 ± 0.20.7 ± 0.10.2 ± 0.0
    Thyroid23.0 ± 6.423.1 ± 12.516.3 ± 9.716.0 ± 2.71.1 ± 0.3
    Lung1.4 ± 0.11.5 ± 0.31.1 ± 0.50.5 ± 0.10.1 ± 0.0
    Heart1.0 ± 0.11.3 ± 0.30.8 ± 0.40.2 ± 0.10.0 ± 0.0
    Muscle0.5 ± 0.20.7 ± 0.20.5 ± 0.20.1 ± 0.10.0 ± 0.0
    Liver1.1 ± 0.21.5 ± 0.40.9 ± 0.50.2 ± 0.10.0 ± 0.0
    Brain0.1 ± 0.00.2 ± 0.10.1 ± 0.00.0 ± 0.00.0 ± 0.0
    Kidney9.5 ± 3.55.8 ± 4.11.9 ± 1.70.5 ± 0.10.1 ± 0.0

    • Data are expressed as percentage injected dose per gram (mean ± SD).

  • TABLE 6

    Biodistribution of 125I-ITAU in Normal Mice (n = 3)

    Organ1 h1.5 h2 h8 h18 h
    Blood3.7 ± 0.44.5 ± 0.33.7 ± 0.80.4 ± 0.10.1 ± 0.1
    Spleen1.6 ± 0.12.3 ± 0.42.1 ± 0.50.2 ± 0.10.1 ± 0.0
    Intestine1.8 ± 0.22.4 ± 0.42.1 ± 0.60.4 ± 0.10.1 ± 0.1
    Thymus2.1 ± 0.53.0 ± 1.02.3 ± 0.60.2 ± 0.20.1 ± 0.0
    Femur1.4 ± 0.11.6 ± 0.11.4 ± 0.30.2 ± 0.10.1 ± 0.0
    Thyroid46.1 ± 5.257.2 ± 10.560.3 ± 27.618.6 ± 13.04.1 ± 2.2
    Lung2.3 ± 0.22.7 ± 0.32.4 ± 0.60.3 ± 0.10.1 ± 0.1
    Heart1.5 ± 0.32.1 ± 0.11.6 ± 0.30.2 ± 0.00.0 ± 0.0
    Muscle0.9 ± 0.11.3 ± 0.11.0 ± 0.20.1 ± 0.00.0 ± 0.0
    Liver1.4 ± 0.22.0 ± 0.21.4 ± 0.40.1 ± 0.00.0 ± 0.0
    Brain0.4 ± 0.00.5 ± 0.10.3 ± 0.10.0 ± 0.00.0 ± 0.0
    Kidney7.2 ± 2.35.0 ± 0.33.6 ± 0.60.3 ± 0.10.1 ± 0.1

    • Data are expressed as percentage injected dose per gram (mean ± SD).

  • TABLE 7

    Urinary Excretion of Iodonucleosides in Normal Mice (n = 3)

    Nucleoside1 h1.5 h2 h8 h18 h
    IUdR18.6 ± 6.721.6 ± 6.623.4 ± 4.548.4 ± 5.754.7 ± 9.1
    ITdU57.5 ± 4.753.6 ± 6.156.5 ± 7.773.1 ± 6.171.4 ± 14.6
    ITAU50.2 ± 5.440.0 ± 7.643.2 ± 6.870.6 ± 3.364.8 ± 5.5

    • Data are expressed as percentage injected dose (mean ± SD).

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