Research ArticleBasic Science Investigations

PET Imaging of Macrophage Mannose Receptor–Expressing Macrophages in Tumor Stroma Using 18F-Radiolabeled Camelid Single-Domain Antibody Fragments

Anneleen Blykers, Steve Schoonooghe, Catarina Xavier, Kevin D’hoe, Damya Laoui, Matthias D’Huyvetter, Ilse Vaneycken, Frederik Cleeren, Guy Bormans, Johannes Heemskerk, Geert Raes, Patrick De Baetselier, Tony Lahoutte, Nick Devoogdt, Jo A. Van Ginderachter and Vicky Caveliers
Journal of Nuclear Medicine August 2015, 56 (8) 1265-1271; DOI: https://doi.org/10.2967/jnumed.115.156828

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    (A) Staining of single-cell suspensions prepared from 15-d-old 3LL-R subcutaneous tumors grown in C57BL/6 WT mice. (B) Staining on immature human dendritic cells expressing human MMR. Shaded histograms represent sdAb BCII10–negative control staining.

  • FIGURE 2.
    FIGURE 2.

    RP-HPLC analysis of purified 18F-FB-anti-MMR 3.49 sdAb (A; γ trace black, left axis; UV trace blue, right axis; retention time = 12.5 min) and after incubation for 3 h in phosphate-buffered saline, pH 7.4, at room temperature (B; γ trace). (C) Reversed-phase chromatogram of urine obtained 30 min after injection of 18F-FB-anti-MMR 3.49 (γ trace).

  • FIGURE 3.
    FIGURE 3.

    Comparison between uptake of 18F-FB-anti-MMR 3.49 sdAb (♦) and 99mTc-anti-MMR 3.49 sdAb (□) in spleen, liver, and tumor 3 h after injection. *Data are significantly different, P < 0.05.

  • FIGURE 4.
    FIGURE 4.

    Transverse and coronal PET/CT images of WT (left) vs. MMR-deficient (right) 3LL-R tumor–bearing mice scanned 3 h after injection of 18F-FB-anti MMR 3.49. PET signals are encoded in color scale, CT image in gray scale. Arrows point to tumor (T), kidney (K), and bladder (B). Autoradiography performed on slices from 3LL-R tumors grown in WT (left) vs. MMR-deficient (right) mice. max = maximum; min = minimum.

Tables

  • TABLE 1

    Binding Kinetics of sdAbs on Human and Mouse MMR

    hMMRmMMR
    sdAbka (M−1 s−1)kd (s−1)KD (nM)ka (M−1 s−1)kd (s−1)KD (nM)
    14.41.4 × 1051.4 × 10−3103.3 × 1042.3 × 10−368
    5.382.0 × 1056.6 × 10−43.31.3 × 1053.3 × 10−325
    26.75.8 × 1057.3 × 10−3136.9 × 1051.3 × 10−31.9
    3.494.4 × 1058.0 × 10−41.82.9 × 1053.6 × 10−312

    • h = human; m = mouse; ka = association rate constant; kd = dissociation rate constant; KD = equilibrium dissociation constant.

  • TABLE 2

    Biodistribution of 99mTc-Anti-MMR sdAbs in 3LL-R–Bearing WT and MMR-KO Mice

    Organ/tissue99mTc-anti-MMR 3.49 WT (n = 3)99mTc-anti-MMR 14.4 WT (n = 3)99mTc-anti-MMR 3.49 MMR-KO (n = 2)
    Heart2.18 ± 0.152.77 ± 0.770.14 ± 0.02
    Lungs1.44 ± 0.150.92 ± 0.280.40 ± 0.08
    Liver14.79 ± 0.5227.37 ± 3.370.61 ± 0.05
    Spleen4.94 ± 0.326.20 ± 1.690.22 ± 0.04
    Kidney146.61 ± 2.8569.30 ± 11.46234.77 ± 25.91
    Muscle0.57 ± 0.140.42 ± 0.110.06 ± 0.02
    Bone1.88 ± 0.171.78 ± 0.810.12 ± 0.01
    Lymph nodes3.04 ± 0.333.02 ± 0.460.19 ± 0.04
    Blood0.30 ± 0.030.13 ± 0.020.18 ± 0.03
    Tumor2.41 ± 0.341.40 ± 0.26Not done

    • Data were obtained at 3 h after injection and expressed as mean %IA/g ± SD.

  • TABLE 3

    Biodistribution of 18F-FB-Anti-MMR 3.49 sdAb in 3LL-R–Bearing WT, MMR-Deficient, and CCR-2–Deficient Mice at 3 Hours After Injection

    Organ/tissueWT mice (n = 8)MMR-KO mice (n = 8)CCR2-KO mice (n = 5)
    Lungs1.60 ± 0.400.82 ± 0.521.45 ± 0.14
    Heart0.81 ± 0.110.28 ± 0.12*1.00 ± 0.14
    Liver2.26 ± 0.510.52 ± 0.30*2.54 ± 0.31
    Spleen1.34 ± 0.310.38 ± 0.16*1.71 ± 0.69
    Kidney7.98 ± 0.864.76 ± 2.767.60 ± 0.76
    Muscle0.37 ± 0.140.10 ± 0.07*0.42 ± 0.27
    Bone0.67 ± 0.280.15 ± 0.02*1.03 ± 0.20
    Blood1.02 ± 0.310.73 ± 0.311.16 ± 0.20
    Tumor2.40 ± 0.460.29 ± 0.14*1.42 ± 0.17†

    • ↵* Data are significantly different, P < 0.05.

    • Data are expressed as mean %IA/g ± SD.

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