OtherBASIC SCIENCE INVESTIGATIONS

Noninternalizing Monoclonal Antibodies Are Suitable Candidates for 125I Radioimmunotherapy of Small-Volume Peritoneal Carcinomatosis

Lore Santoro, Samir Boutaleb, Véronique Garambois, Caroline Bascoul-Mollevi, Vincent Boudousq, Pierre-Olivier Kotzki, Monique Pèlegrin, Isabelle Navarro-Teulon, André Pèlegrin and Jean-Pierre Pouget
Journal of Nuclear Medicine December 2009, 50 (12) 2033-2041; DOI: https://doi.org/10.2967/jnumed.109.066993

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    Tumor growth and bioluminescence calibration curves. (A) Swiss nude mice bearing 1- to 2-mm xenograft A-431 tumor nodules were followed by bioluminescence imaging. Flow cytometry analysis (inset) indicated similar levels of expression of EGFR and CEA receptors at surface of A-431 cells. (B) In vivo relationship between bioluminescence signal and mean tumor weight per mouse. Ph/s = photons/s.

  • FIGURE 2. 
    FIGURE 2. 

    Swiss nude mice bearing intraperitoneal A-431 tumor cell xenografts were injected twice with 37 MBq of 125I-mAbs (370 MBq/mg) or with unlabeled mAbs (100 μg). (A) Noninternalizing 35A7 mAbs. (B) Internalizing m225 mAbs. (C) Irrelevant PX mAbs. Untreated controls were injected with NaCl. Tumor growth was followed by bioluminescence imaging. Corresponding mean tumor weights were next calculated using calibration curve reported in Figure 1B, and they are shown as function of time in A, B, C, respectively.

  • FIGURE 3. 
    FIGURE 3. 

    Swiss nude mice bearing intraperitoneal A-431 tumor cell xenografts were intravenously injected twice with 37 MBq of 125I-mAbs (370 MBq/mg) or with unlabeled mAb (100 μg). (A) Noninternalizing 35A7 mAbs. (B) Internalizing m225 mAbs. (C) Irrelevant PX mAb. Survival rates were estimated using Kaplan–Meier method. Mice were sacrificed when bioluminescence signal reached 4.5 × 107 photons/s. Censored mice are indicated on graph by vertical bars.

  • FIGURE 4. 
    FIGURE 4. 

    Biodistribution. Swiss nude mice bearing intraperitoneal A-431 tumor cell xenografts were intravenously injected twice with solution containing specific 125I-mAbs or irrelevant131I-PX. %IA/g was determined in healthy organs and tumors. (A) Noninternalizing 125I-mAbs. (B) Internalizing 125I-mAbs. Four mice were analyzed at each time point.

  • FIGURE 5. 
    FIGURE 5. 

    Uptake of radioactivity. Uptake of radioactivity per tissue (becquerel) was determined using values obtained during biodistribution experiments (Fig. 4). (A) Noninternalizing 125I-mAbs. (B) Internalizing 125I-mAbs.

  • FIGURE 6. 
    FIGURE 6. 

    MIRD dose calculation. From Figure 5, total cumulative decays per tissue, Ã, was calculated by measuring area under each curve. Ã was next multiplied by 19.483 keV, corresponding to mean energy delivered at each 125I decay.

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