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OtherBasic Science Investigations

123I-Labeled Chitinase as Specific Radioligand for In Vivo Detection of Fungal Infections in Mice

Rien Siaens, Vincent G.H. Eijsink, Rudi Dierckx and Guido Slegers
Journal of Nuclear Medicine July 2004, 45 (7) 1209-1216;
Rien Siaens
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Vincent G.H. Eijsink
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Rudi Dierckx
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Guido Slegers
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  • FIGURE 1.
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    FIGURE 1.

    Stability of 123I-ChiB_E144Q in PBS as determined by ITLC (n = 5). ▵, in serum; ▪, in PBS.

  • FIGURE 2.
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    FIGURE 2.

    Typical UV profile (280 nm) of unlabeled ChiB_E144Q (upside down) combined with radiogram of 123I-ChiB_E144Q.

  • FIGURE 3.
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    FIGURE 3.

    In vitro accumulation of 123I-ChiB_E144Q in various organisms after 24-h incubation at 4°C. Amount of tracer bound per 1 × 107 cfu is plotted as function of increasing amounts of added tracer (1 μL = 2 × 103 Bq). ▪, C. albicans; ○, E. coli; ▵, A. fumigatus; ×, S. aureus.

  • FIGURE 4.
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    FIGURE 4.

    In vivo blood clearance (%ID) in healthy NMRI mice until 48 h after injection. Half-life (t1/2) parameters are calculated. Blood clearance follows a biexponential curve with equation (r2 = 0.987): A = A1 exp(−λ1t) + A2 exp(−λ2t) with t1/2,1 = 0.144 ± 0.035, t1/2,2 = 4.229 ± 0.701 and A1 = 6.436 ± 0.700 (%ID) and A2 = 9.053 ± 0.661 (%ID), λ1 = 0.1011 ± 0.0309 (min−1), λ2 = 0.0027 ± 0.0309 (min−1).

  • FIGURE 5.
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    FIGURE 5.

    Scintigraphic images of nu/nu mice (n = 4) with unilateral infections of 1 × 107 conidia of A. candida (A) and 1 × 107 cfu of S. aureus (B) 24 h after injection of 7.4 MBq in 100 μL of 123I-ChiB_E144Q. Arrows indicate site of infection. 1 = thyroid; 2 = stomach; 3 = bladder.

  • FIGURE 6.
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    FIGURE 6.

    Uptake expressed as T/NT ratio ± SD (n = 3) of 123I-ChiB_E144Q in E. coli infections (▵) and C. albicans infections (♦) until 24 h after infection.

  • FIGURE 7.
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    FIGURE 7.

    Relation between number of injected viable C. albicans and accumulation of 123I-ChiB_E144Q, expressed as T/NT ratio in infected tissue in Swiss nu/nu mice (n = 3).

Tables

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    TABLE 1

    Various Reaction Times and Corresponding Labeling Efficiency of 123I-ChiB_E144Q

    Reaction time (min)Radiochemical yield (%)
    510.81
    1034.87
    1041.64
    1034.95
    2044.49
    3040.31
    • View popup
    TABLE 2

    Binding of 123I-ChiB_E144Q to Mammalian Cells In Vivo at Different Time Points

    Fraction1 h4 h8 h18 h24 h24 h*
    Erythrocyte0.140.100.090.090.070.35
    Leucocyte0.020.040.020.070.020.45
    Protein2.822.193.353.913.201.12
    Free 123I0.040.060.050.060.050.65
    • ↵* Distribution data at 24 h after injection of free 123I as control.

    • Data are expressed as % activity/% (g) blood.

    • View popup
    TABLE 3

    Biodistribution Results of 123I-ChiB_E144Q in Noninfected NMRI Mice

    Biodistribution20 min1 h4 h9 h24 h48 h
    Blood14.23 ± 3.8013.37 ± 1.015.09 ± 1.543.62 ± 0.430.83 ± 0.110.20 ± 0.03
    Brain0.29 ± 0.120.30 ± 0.080.18 ± 0.150.11 ± 0.020.03 ± 0.030.03 ± 0.04
    Heart3.80 ± 1.434.89 ± 1.851.40 ± 0.531.17 ± 0.400.35 ± 0.060.18 ± 0.13
    Lung5.01 ± 3.595.86 ± 1.401.86 ± 0.700.92 ± 1.170.42 ± 0.110.14 ± 0.04
    Stomach1.96 ± 1.304.89 ± 3.138.78 ± 4.106.64 ± 6.670.55 ± 0.120.11 ± 0.12
    Spleen3.69 ± 0.553.18 ± 0.231.23 ± 0.510.95 ± 0.050.22 ± 0.030.09 ± 0.06
    Liver2.32 ± 0.431.92 ± 0.900.99 ± 0.360.66 ± 0.120.19 ± 0.010.07 ± 0.01
    Kidneys5.23 ± 1.855.20 ± 0.932.18 ± 0.551.39 ± 0.270.45 ± 0.280.18 ± 0.09
    Small intestine0.72 ± 0.201.54 ± 0.111.00 ± 0.210.50 ± 0.570.14 ± 0.010.04 ± 0.02
    Large intestine0.52 ± 0.200.79 ± 0.210.88 ± 0.040.65 ± 0.710.11 ± 0.050.05 ± 0.01
    Bladder6.40 ± 4.401.62 ± 0.382.93 ± 2.011.57 ± 1.140.44 ± 0.330.44 ± 0.31
    Fatty tissue1.55 ± 0.531.19 ± 1.121.16 ± 0.890.53 ± 0.220.22 ± 0.060.10 ± 0.03
    • Data are expressed as %ID/g ± SD (n = 3 mice/group). Represented data are a selection from 19 different time points ranging from 20 s to 48 h.

    • View popup
    TABLE 4

    Biodistribution Data of 123I-ChiB_E144Q in Infected nu/nu Mice 24 h After Injection

    BiodistributionC. albicansA. fumigatusE. coliS. aureusSterile inflammationA. fumigatus*
    Blood0.70 ± 0.020.66 ± 0.050.92 ± 0.590.72 ± 0.130.66 ± 0.050.99 ± 0.31
    Muscle0.09 ± 0.010.11 ± 0.080.24 ± 0.160.10 ± 0.020.11 ± 0.080.27 ± 0.10
    Abscess1.91 ± 0.132.07 ± 0.010.47 ± 0.310.46 ± 0.260.60 ± 0.060.47 ± 0.19
    Lung0.37 ± 0.090.31 ± 0.020.42 ± 0.140.45 ± 0.040.47 ± 0.020.87 ± 0.07
    Spleen0.26 ± 0.030.18 ± 0.020.24 ± 0.030.31 ± 0.050.16 ± 0.026.37 ± 1.29
    Kidney0.61 ± 0.130.29 ± 0.040.41 ± 0.100.52 ± 0.100.26 ± 0.053.28 ± 1.08
    Liver0.35 ± 0.010.22 ± 0.020.23 ± 0.040.38 ± 0.050.16 ± 0.0216.32 ± 3.83
    Intestine0.27 ± 0.040.07 ± 0.020.21 ± 0.090.23 ± 0.030.08 ± 0.020.41 ± 0.11
    Bladder1.60 ± 0.580.73 ± 0.330.57 ± 0.270.62 ± 0.270.41 ± 0.321.29 ± 0.32
    Stomach3.06 ± 1.570.82 ± 0.253.48 ± 2.552.47 ± 0.480.74 ± 0.252.16 ± 1.38
    • ↵* Results of 123I-BSA in A. fumigatus infection.

    • Data are expressed as %ID/g ± SD (n = 4 mice/group).

    • View popup
    TABLE 5

    Comparison of T/NT and Target-to-Blood Ratios as Calculated from Biodistribution Data of Different Radioligands in Infected nu/nu Mice 24 h After Injection

    Infection123I-ChiB_E144Q123I-BSA67Ga Citrate
    C. albicans
     Muscle20.62 ± 3.062.11 ± 0.574.83 ± 0.48
     Blood2.72 ± 0.250.59 ± 0.111.57 ± 0.07
    A. fumigatus
     Muscle15.16 ± 3.721.44 ± 1.695.59 ± 2.72
     Blood1.47 ± 0.220.60 ± 0.793.06 ± 1.26
    E. coli
     Muscle3.03 ± 2.301.69 ± 0.893.11 ± 1.28
     Blood0.57 ± 0.400.34 ± 0.141.43 ± 0.49
    S. aureus
     Muscle4.86 ± 2.62NDND
     Blood0.62 ± 0.24NDND
    Sterile inflam.
     Muscle5.31 ± 2.83NDND
     Blood0.91 ± 0.81NDND
    • ND = not determined; inflam. inflammation.

    • Data are expressed as %ID/g ± SD (n = 4 mice/group).

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Journal of Nuclear Medicine: 45 (7)
Journal of Nuclear Medicine
Vol. 45, Issue 7
July 1, 2004
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123I-Labeled Chitinase as Specific Radioligand for In Vivo Detection of Fungal Infections in Mice
Rien Siaens, Vincent G.H. Eijsink, Rudi Dierckx, Guido Slegers
Journal of Nuclear Medicine Jul 2004, 45 (7) 1209-1216;

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123I-Labeled Chitinase as Specific Radioligand for In Vivo Detection of Fungal Infections in Mice
Rien Siaens, Vincent G.H. Eijsink, Rudi Dierckx, Guido Slegers
Journal of Nuclear Medicine Jul 2004, 45 (7) 1209-1216;
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