Research ArticleBasic Science Investigations

Photoimmunotherapy Targeting Prostate-Specific Membrane Antigen: Are Antibody Fragments as Effective as Antibodies?

Rira Watanabe, Hirofumi Hanaoka, Kazuhide Sato, Tadanobu Nagaya, Toshiko Harada, Makoto Mitsunaga, Insook Kim, Chang H. Paik, Anna M. Wu, Peter L. Choyke and Hisataka Kobayashi
Journal of Nuclear Medicine January 2015, 56 (1) 140-144; DOI: https://doi.org/10.2967/jnumed.114.149526

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Differential interference contrast and fluorescence microscopy of photoimmunotherapy-treated mix of PC3pip (PSMA-positive) and flu (PSMA-negative) cells. Cells were incubated with anti-PSMA antibodies (IgG-IR700), Mbs (Mb-IR700), or Dbs (Db-IR700) at 10 μg/mL. Just after fluorescence imaging, only PSMA-positive cells demonstrate necrotic cell death (cell budding/rupture). Scale bar = 50 μm. PIT = photoimmunotherapy.

  • FIGURE 2.
    FIGURE 2.

    Target-specific cell death in response to IgG-, Mb-, or Db-IR700–mediated photoimmunotherapy in PSMA-positive (A) or -negative (B) cells. Target-specific cell death in response to photoimmunotherapy was dose-dependent to intensity of irradiation. Data are mean ± SEM (n ≥ 3).

  • FIGURE 3.
    FIGURE 3.

    Analysis of in vivo biodistribution of radioactivity after injection of 125I-PSMA-IgG (A), Mb (B), or Db (C) into mice bearing PSMA positive (PSMA+) and negative (PSMA−) tumors. Each value was calculated using percentage injected dose per gram of tissue (Supplemental Fig. 1) for each animal and represented as mean ± SEM (n = 3–5): ratios of each organ and tumor to blood (left), subtraction of PSMA-negative tumor from PSMA-positive tumor (center), and ratios of PSMA-positive tumor to PSMA-negative tumor (right). * = value cannot be calculated because some denominators are 0.

  • FIGURE 4.
    FIGURE 4.

    Tumor volume and survival curves of PSMA-positive tumor-bearing mice. Mice were randomized to 1 of 3 groups at 3 d after tumor cell injection (n = 9–10). IgG-IR700 (A), Mb-IR700 (B), or Db-IR700 (C) was injected, and photoimmunotherapy was performed at 1 and 2 d after injection for IgG-IR700 or Mb-IR700 and at 6 h and 1 d after injection of Db-IR700. Mice were observed until tumor volume reached more than 500 mm3, at which time mice had to be euthanized. *P < 0.05 vs. control, Dunnett multiple-comparison test. #P < 0.05 vs. control, log-rank test. Ab = antibody.

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