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Research ArticleBasic Science Investigation

Copolymer-Based Hepatocyte Asialoglycoprotein Receptor Targeting Agent for SPECT

Wenjiang Yang, Tiantian Mou, Guoqiang Shao, Feng Wang, Xianzhong Zhang and Boli Liu
Journal of Nuclear Medicine June 2011, 52 (6) 978-985; DOI: https://doi.org/10.2967/jnumed.110.085167
Wenjiang Yang
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Tiantian Mou
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Guoqiang Shao
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Feng Wang
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Xianzhong Zhang
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Boli Liu
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  • FIGURE 1.
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    FIGURE 1.

    Synthesis route of copolymer P(VLA-co-VNI) with galactose and hydrazinonicotinamide group (ratio of VLA units to VNI units was about 94:6 according to the carbon-to-nitrogen (C/N) mass ratio of P(VLA-co-VNI)). AIBN = azobisisobutyronitrile.

  • FIGURE 2.
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    FIGURE 2.

    High-performance liquid chromatograms of 99mTc[P(VLA-co-VNI)](tricine)2. Retention time was 11.9 min both after storage in saline at room temperature for 4 h and after incubation in murine plasma at 37°C for 4 h, indicating the high stability of 99mTc[P(VLA-co-VNI)](tricine)2 in vitro.

  • FIGURE 3.
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    FIGURE 3.

    HPLC profiles of metabolic stability of 99mTc[P(VLA-co-VNI)](tricine)2. Liver was collected at 10 and 120 min after injection of 99mTc[P(VLA-co-VNI)](tricine)2, blood was collected at 10 min after injection, and urine was collected at 120 min after injection. 99mTc[P(VLA-co-VNI)](tricine)2 was intact in liver at 10 and 120 min after injection (A and C), with retention time of 11.9 min. Retention times of blood (B) and urine (D) samples were 11.9 and 18.8 min, respectively.

  • FIGURE 4.
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    FIGURE 4.

    Time–activity curves obtained from 15-min dynamic planar acquisition. (A) In normal rabbit, liver uptake peaked rapidly within 2.5–5 min, whereas radioactivity in blood decreased rapidly. (B) In blocking study, uptake rate in liver was significantly reduced by preinjected neogalactosylalbumin. Uptake in blood and kidneys was relatively high and decreased continuously over time.

  • FIGURE 5.
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    FIGURE 5.

    Planar images of rabbit. The upper row is control group; lower row is blocking group with free neogalactosylalbumin as blocking agent (10 mg/kg of rabbit body weight). Times are times after injection.

  • FIGURE 6.
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    FIGURE 6.

    SPECT/CT for detection and localization of liver cancer. Liver is visualized as transaxial sections at 30 min after injection merged with CT and SPECT images. Arrows indicate site of tumor.

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    TABLE 1

    Biodistribution of 99mTc[P(VLA-co-VNI)](tricine)2 in Normal Mice

    Control (min)Block with P(VLA-co-VNI) (min)Block with neogalactosylalbumin (min)
    103012010301201030120
    Heart0.71 ± 0.130.71 ± 0.180.62 ± 0.176.69 ± 2.110.62 ± 0.310.65 ± 0.193.19 ± 0.591.11 ± 0.411.10 ± 0.25
    Liver125.33 ± 10.99122.64 ± 9.06114.74 ± 9.9334.12 ± 3.2467.81 ± 5.2863.33 ± 5.2158.05 ± 5.2775.30 ± 4.9956.45 ± 8.53
    Lung0.88 ± 0.240.76 ± 0.240.42 ± 0.1814.79 ± 5.220.87 ± 0.190.70 ± 0.279.19 ± 1.040.83 ± 0.200.96 ± 0.36
    Kidney2.42 ± 0.352.92 ± 0.822.40 ± 0.6614.70 ± 3.485.33 ± 0.574.50 ± 0.7310.28 ± 1.154.50 ± 0.745.08 ± 0.62
    Spleen1.92 ± 0.912.53 ± 1.131.35 ± 0.714.49 ± 1.230.61 ± 0.080.54 ± 0.126.71 ± 1.406.56 ± 1.556.89 ± 2.47
    Stomach0.51 ± 0.240.88 ± 0.240.52 ± 0.230.30 ± 0.080.22 ± 0.060.77 ± 0.460.23 ± 0.130.25 ± 0.140.32 ± 0.12
    Blood0.23 ± 0.070.07 ± 0.010.02 ± 0.0130.48 ± 7.180.15 ± 0.030.04 ± 0.0016.55 ± 2.600.16 ± 0.070.03 ± 0.00
    Bone1.02 ± 0.280.98 ± 0.180.86 ± 0.314.74 ± 1.000.91 ± 0.131.02 ± 0.413.50 ± 0.621.73 ± 0.462.37 ± 0.74
    Muscle0.38 ± 0.080.51 ± 0.270.43 ± 0.111.28 ± 0.500.54 ± 0.170.39 ± 0.110.81 ± 0.180.47 ± 0.230.55 ± 0.30
    Small intestine0.85 ± 0.302.93 ± 2.491.46 ± 0.351.79 ± 0.371.93 ± 0.210.88 ± 0.281.38 ± 0.081.92 ± 0.721.03 ± 0.27
    • Data are biodistribution 10, 30, and 120 min after intravenous injection of 99mTc[P(VLA-co-VNI)](tricine)2 into normal mice, and results of blocking experiment with preinjection of free neogalactosylalbumin or P(VLA-co-VNI) as inhibitor. Data are expressed as mean %ID/g ± SD (n = 5).

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Journal of Nuclear Medicine: 52 (6)
Journal of Nuclear Medicine
Vol. 52, Issue 6
June 1, 2011
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Copolymer-Based Hepatocyte Asialoglycoprotein Receptor Targeting Agent for SPECT
Wenjiang Yang, Tiantian Mou, Guoqiang Shao, Feng Wang, Xianzhong Zhang, Boli Liu
Journal of Nuclear Medicine Jun 2011, 52 (6) 978-985; DOI: 10.2967/jnumed.110.085167

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Copolymer-Based Hepatocyte Asialoglycoprotein Receptor Targeting Agent for SPECT
Wenjiang Yang, Tiantian Mou, Guoqiang Shao, Feng Wang, Xianzhong Zhang, Boli Liu
Journal of Nuclear Medicine Jun 2011, 52 (6) 978-985; DOI: 10.2967/jnumed.110.085167
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