Research ArticleClinical Investigations

N-(4-18F-Fluorobenzoyl)Interleukin-2 for PET of Human-Activated T Lymphocytes

Valentina Di Gialleonardo, Alberto Signore, Andor W.J.M. Glaudemans, Rudi A.J.O. Dierckx and Erik F.J. De Vries
Journal of Nuclear Medicine May 2012, 53 (5) 679-686; DOI: https://doi.org/10.2967/jnumed.111.091306

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    MALDI-TOF profile of 18F-FB-IL2.

  • FIGURE 2.
    FIGURE 2.

    MTT cell proliferation assay of phytohemoagglutinin-activated hPBMc stimulated by native IL2 or 18F-FB-IL2. Results are expressed as percentage of increase in cellular proliferation as compared with untreated cells (mean ± SD of 3 independent experiments, each performed in triplicate). There is no significant difference between labeled and unlabeled IL2 at any tested concentration.

  • FIGURE 3.
    FIGURE 3.

    3-chloroacetic acid precipitation assay as percentage of labeled IL2 at different times in phosphate-buffered saline and human plasma. PBS = phosphate-buffered saline.

  • FIGURE 4.
    FIGURE 4.

    Small-animal PET images of SCID mice inoculated with phytohemoagglutinin-activated T lymphocytes. Small-animal PET image (transaxial section of mouse shoulders) shows 18F-FB-IL2 uptake in right shoulder (red arrow) and, to lesser extent, in contralateral, control shoulder (yellow arrow) due to migration of lymphocytes from injection site to contralateral site.

  • FIGURE 5.
    FIGURE 5.

    (A) Visual inspection of derma of inoculated mouse, of which PET image is presented in Figure 4. Red arrow highlights site at which lymphocytes were inoculated with Matrigel in right shoulder, and yellow arrow indicates inflammatory reaction after inoculation of Matrigel only in left shoulder. (B) Hematoxylin and eosin staining of skin from left shoulder showing presence of lymphocytes at border of Matrigel (black arrows).

  • FIGURE 6.
    FIGURE 6.

    Correlation between number of inoculated lymphocytes and 18F-FB-IL2 uptake in both shoulders (R2 = 0.768, P = 0.0012).

  • FIGURE 7.
    FIGURE 7.

    In vivo binding of 18F-FB-IL2 to 10 × 106 phytohemoagglutinin-activated T lymphocytes inoculated in shoulder of SCID mice (n = 4) (left bar) and in mice (n = 4) pretreated with 100-fold excess of unlabeled IL2 (right bar). Data are mean ± SD of standardized uptake value calculated 30 min after radiopharmaceutical injection.

Tables

  • TABLE 1

    Biodistribution of Radiotracer 18F-FB-IL2 in 12 BALB/c Mice at Different Time Points

    Organ15 min (n = 4)60 min (n = 4)90 min (n = 4)
    Bone8.35 ± 7.792.86 ± 4.053.48 ± 3.01
    Cerebellum1.40 ± 0.950.53 ± 0.780.55 ± 0.22
    Cerebrum0.93 ± 0.680.51 ± 0.750.37 ± 0.09
    Colon3.09 ± 2.501.38 ± 1.792.95 ± 1.65
    Duodenum30.87 ± 23.9612.49 ± 6.107.56 ± 11.82
    Heart3.01 ± 2.871.78 ± 2.441.01 ± 0.13
    Ileum9.46 ± 13.281.54 ± 2.172.93 ± 1.36
    Kidney52.68 ± 55.3921.64 ± 28.7030.82 ± 17.87
    Liver5.76 ± 4.913.51 ± 5.262.67 ± 0.87
    Lung4.37 ± 3.203.75 ± 4.414.89 ± 5.65
    Muscle5.11 ± 3.210.89 ± 1.195.05 ± 4.42
    Pancreas2.06 ± 1.591.41 ± 1.961.04 ± 0.25
    Plasma12.18 ± 11.446.96 ± 9.493.44 ± 1.14
    Red blood cells4.20 ± 3.922.80 ± 3.951.85 ± 0.35
    Spleen1.26 ± 0.551.46 ± 2.101.40 ± 0.53
    Stomach2.44 ± 1.190.26 ± 0.152.67 ± 2.81

    • Data are %ID/g, as mean ± SD.

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