Research ArticleBasic Science Investigations

Stratification of 18F-Labeled PET Imaging Agents for the Assessment of Antiangiogenic Therapy Responses in Tumors

Julian L. Goggi, Romain Bejot, Shehzahdi S. Moonshi and Kishore K. Bhakoo
Journal of Nuclear Medicine September 2013, 54 (9) 1630-1636; DOI: https://doi.org/10.2967/jnumed.112.115824

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Growth kinetics of U87-MG tumors (A) and MDA-MB-231 tumors (B) in vehicle-treated animals and axitinib-treated animals (volume is reported in mm3 [mean ± SD; n = 4]). Arrows denote day 0, 1 d before initiation of therapy regimen. *P < 0.05. **P < 0.01.

  • FIGURE 2.
    FIGURE 2.

    Uptake of 18F-FDG in U87-MG tumors (A; n = 7) and MDA-MB-231 tumors (B; n = 4) in vehicle-treated animals and axitinib-treated animals, normalized to day 0 (% normalized uptake from day 0 [mean ± SD]). **P < 0.01.

  • FIGURE 3.
    FIGURE 3.

    Uptake of 18F-FLT in U87-MG tumors (A; n = 7) and MDA-MB-231 tumors (B; n = 4) in vehicle-treated animals and axitinib-treated animals, normalized to day 0 (% normalized uptake from day 0 [mean ± SD]). *P < 0.05. **P < 0.01.

  • FIGURE 4.
    FIGURE 4.

    Uptake of 18F-FtRGD in U87-MG tumors (A; n = 4) and MDA-MB-231 tumors (B; n = 7) in vehicle-treated animals and axitinib-treated animals, normalized to day 0 (% normalized uptake from day 0 [mean ± SD]). *P < 0.05. **P < 0.01.

  • FIGURE 5.
    FIGURE 5.

    Angiogenesis (represented by MVD) in U87-MG and MDA-MB-231 tumors. MVD was significantly lower in both U87-MG tumors (A; n = 10) and MDA-MB-231 tumors (B; n = 10) from axitinib-treated mice than in tumors from vehicle-treated mice 10 d after treatment initiation. Data are reported as percentage difference in CD34-positive (CD34+ve) staining per square millimeter, normalized to average for vehicle-treated specimens. *P < 0.05. **P < 0.01.

  • FIGURE 6.
    FIGURE 6.

    Representative sections were taken from both tumor types 10 d after initiation of therapy regimen. Representative sections from axitinib-treated U87-MG tumors (A) and MDA-MB-231 tumors (C) were analyzed for MVD after staining for endothelial cells with CD34 (bars = 100 μm) and compared with sections from vehicle-treated U87-MG tumors (B) and MDA-MB-231 tumors (D).

  • FIGURE 7.
    FIGURE 7.

    Rate of proliferation (Ki67) of U87-MG and MDA-MB-231 tumors. Ki67 levels were significantly lower in both U87-MG tumors (A; n = 6) and MDA-MB-231 tumors (B; n = 6) from axitinib-treated mice than in tumors from vehicle-treated mice 10 d after treatment initiation. Data are reported as percentage difference in Ki67-positive (Ki67+ve) cells per square millimeter, normalized to average for vehicle-treated specimens. *P < 0.05. **P < 0.01.

Tables

  • TABLE 1

    Uptake of 18F-FDG in U87-MG (n = 7) and MDA-MB-231 (n = 4) Tumors

    Uptake (mean ± SD %ID/g) of 18F-FDG in:
    U87-MG tumorsMDA-MB-231 tumors
    Days after treatmentAxitinib treatedVehicle treatedAxitinib treatedVehicle treated
    03.03 ± 0.462.99 ± 0.311.84 ± 0.102.05 ± 0.16
    13.07 ± 0.623.24 ± 0.331.93 ± 0.192.09 ± 0.17
    33.76 ± 1.104.29 ± 0.601.98 ± 0.122.25 ± 0.19
    73.66 ± 0.834.94 ± 1.201.79 ± 0.052.25 ± 0.20
    103.68 ± 0.415.26 ± 0.481.54 ± 0.072.22 ± 0.21
  • TABLE 2

    Uptake of 18F-FLT in U87-MG (n = 7) and MDA-MB-231 (n = 4) Tumors

    Uptake (mean ± SD %ID/g) of 18F-FLT in:
    U87-MG tumorsMDA-MB-231 tumors
    Days after treatmentAxitinib treatedVehicle treatedAxitinib treatedVehicle treated
    03.02 ± 1.182.82 ± 0.693.37 ± 0.332.90 ± 0.46
    13.47 ± 1.234.3 ± 0.143.28 ± 0.293.08 ± 0.53
    33.37 ± 0.844.9 ± 0.682.54 ± 0.242.89 ± 0.83
    72.65 ± 0.604.14 ± 0.561.99 ± 0.683.29 ± 0.53
    103.34 ± 0.604.68 ± 0.891.84 ± 0.503.30 ± 0.55
  • TABLE 3

    Uptake of 18F-FtRGD in U87-MG (n = 4) and MDA-MB-231 (n = 7) Tumors

    Uptake (mean ± SD %ID/g) of 18F-FtRGD in:
    U87-MG tumorsMDA-MB-231 tumors
    Days after treatmentAxitinib treatedVehicle treatedAxitinib treatedVehicle treated
    01.62 ± 0.321.50 ± 0.251.59 ± 0.721.58 ± 0.41
    11.66 ± 0.231.74 ± 0.291.69 ± 0.171.71 ± 0.14
    31.37 ± 0.291.61 ± 0.431.07 ± 0.281.36 ± 0.06
    71.43 ± 0.222.40 ± 0.562.01 ± 0.541.90 ± 0.59
    101.65 ± 0.253.33 ± 0.631.28 ± 0.061.50 ± 0.03
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