OtherBASIC SCIENCE INVESTIGATIONS

PET Imaging of VPAC1 Expression in Experimental and Spontaneous Prostate Cancer

Kaijun Zhang, Mohan R. Aruva, Nylla Shanthly, Christopher A. Cardi, Satish Rattan, Chirag Patel, Christopher Kim, Peter A. McCue, Eric Wickstrom and Mathew L. Thakur
Journal of Nuclear Medicine January 2008, 49 (1) 112-121; DOI: https://doi.org/10.2967/jnumed.107.043703

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    Schematic presentation of Cu-TP3939 (A) and HPLC eluates of 64Cu-TP3939 at 6.7 min and free 64Cu at 3.9 min (B). Diagonal line represents gradient.

  • FIGURE 2. 
    FIGURE 2. 

    Muscle relaxivity assays as function of concentration for VIP28 and its analogue TP3939. IC50 values are calculated as concentration at which 50% relaxivity occurred.

  • FIGURE 3. 
    FIGURE 3. 

    Scatchard plots for 99mTc-TP3939 binding to PC3 cells known to express VPAC1 oncogene receptors. Kd value was 0.77 × 10−9 M.

  • FIGURE 4. 
    FIGURE 4. 

    64CuCl2 binding assays for PC3 cells performed with added copper carrier (B and D) and with no 64CuCl2 carrier added (A and C). In either case, data reveal nonsaturable, nonspecific binding.

  • FIGURE 5. 
    FIGURE 5. 

    Blood clearance curve of 64Cu-TP3939 in athymic nude mice (n = 3).

  • FIGURE 6. 
    FIGURE 6. 

    Autoradiography (A) and gel stained with Coomassie blue (B) after PAGE analysis of serum isolated from mouse after intravenous administration of 64Cu-TP3939. Lane 1 (L1) = 64Cu-TP3939 in mouse serum; lane 2 (L2) = 64Cu-TP3939 with human serum albumin; lane 3 (L3) = 64CuCl2 with human serum albumin; lane 4 (L4) = 64CuCl2; STD = molecular weight standard.

  • FIGURE 7. 
    FIGURE 7. 

    (A) Transaxial PET images demonstrate high uptake of 64Cu-TP3939 in xenografted PC3 tumor in right flank of athymic nude mouse (dashed arrows). Images were taken 4 and 24 h after injection of 64Cu-TP3939. (B) Presented from left to right are composite of 18F-FDG, CT, and 64Cu-TP3939 images obtained from TRAMP I and TRAMP II transgenic mice and histology of their corresponding prostate glands. One-hour 18F-FDG images show only bladder activity (solid arrow). In 4-h CT images, dashed and solid arrows show prostate and bladder, respectively. Four-hour 64Cu-TP3939 transaxial PET images show only colon activity (oval-head arrow) in TRAMP I, whereas in TRAMP II, significant PC uptake (dashed arrow) and negligible colon uptake are seen. Prostate histology (×40) indicates grade II and grade IV prostate intraepithelial neoplasia in TRAMP I and TRAMP II, respectively (black arrows). Tumor with histology grade IV is visible with 64Cu-TP3939 but not with 18F-FDG.

Tables

  • TABLE 1

    IC50 and Kd Values

    PeptideIC50Kd
    TP39394.4 × 10−8 M0.77 × 10−9 M
    VIP289.1 × 10−8 M15.0 × 10−9 M
  • TABLE 2

    PAGE Analysis: Estimated Molecular Weights and % Radioactivity Associated with Them

    Molecular weight (kDa)Lane 1: 64Cu-TP3939 in serum (in vivo) (%)Lane 2: 64Cu-TP3939 with HAS (%)Lane 3: 64CuCl2 with HAS (%)Lane 4: 64CuCl2 (%)
    >9810.080.472.252.46
    50–644.030.250.170.38
    6–161.230.090.160.45
    <4–483.9199.1997.4296.74

    • HSA = human serum albumin.

  • TABLE 3

    Tissue Distribution (%ID/g) of 64Cu-TP3939 in PC3 Tumor-Bearing Nude Mice (n = 5)

    Tissue4 h24 hP
    Muscle1.94 ± 0.851.15 ± 0.180.17
    Intestine11.00 ± 1.647.67 ± 2.480.06
    Heart9.13 ± 5.634.14 ± 0.650.19
    Lungs34.31 ± 9.7619.93 ± 5.560.06
    Blood3.85 ± 1.142.38 ± 0.260.07
    Spleen19.22 ± 9.133.56 ± 0.380.03
    Kidneys18.38 ± 9.9510.06 ± 0.420.21
    Liver55.00 ± 12.6227.58 ± 2.180.01
    Tumor7.48 ± 3.635.78 ± 0.660.47
    T/M ratio3.98 ± 1.435.17 ± 1.320.29
    T/B ratio1.94 ± 0.662.46 ± 0.450.28
  • TABLE 4

    Tissue Distribution (%ID/g) of 64CuCl2 in PC3 Tumor-Bearing Nude Mice (n = 5)

    Tissue4 h24 hP
    Muscle0.69 ± 0.210.86 ± 0.100.14
    Intestine8.84 ± 1.304.58 ± 0.760.00
    Heart3.66 ± 0.433.38 ± 0.280.25
    Lungs10.17 ± 1.956.32 ± 1.570.01
    Blood1.73 ± 0.301.32 ± 0.140.03
    Spleen2.26 ± 0.211.84 ± 0.320.04
    Kidneys9.18 ± 0.798.38 ± 1.470.32
    Liver19.30 ± 4.3719.95 ± 4.520.82
    Tumor4.79 ± 0.344.03 ± 0.830.10
    T/M ratio7.40 ± 1.714.73 ± 1.190.02
    T/B ratio2.81 ± 0.333.04 ± 0.430.37
  • TABLE 5

    Tissue Distribution (%ID/g) of 64Cu-TP3939 in Mice Bearing PC3 Xenografts (n = 5, 24 h)

    TissueReceptors unblockedReceptors blockedP
    Muscle1.15 ± 0.180.65 ± 0.110.01
    Intestine7.67 ± 2.483.90 ± 0.500.01
    Heart4.14 ± 0.652.70 ± 0.640.02
    Lungs19.93 ± 5.567.01 ± 2.790.01
    Blood2.38 ± 0.261.35 ± 0.300.01
    Spleen3.56 ± 0.381.60 ± 0.240.01
    Kidneys10.06 ± 0.425.24 ± 0.960.01
    Liver27.58 ± 2.1812.44 ± 3.570.01
    Tumor5.78 ± 0.661.84 ± 0.440.01
    T/M ratio5.17 ± 1.322.91 ± 0.910.03
    T/B ratio2.46 ± 0.451.43 ± 0.560.04

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