In Vivo Evaluation of 111In-Labeled T-Lymphocyte Homing in Experimental Colitis
Catherine van Montfrans, MD, PhD1,
Roelof J. Bennink, MD, PhD2,
Kora de Bruin2,
Wouter de Jonge, PhD3,
Hein J. Verberne, MD2,
Fiebo J.W. ten Kate, MD, PhD4,
Sander J.H. van Deventer, MD, PhD3 and
Anje A. te Velde, PhD1
1 Department of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
2 Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands
3 Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
4 Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
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FIGURE 1. Colon radioactivity uptake is increased in mice with TNBS colitis transferred with TNBS-sensitized 111In-labeled lymphocytes. SPECT was performed 48 h after transfer of 111In-labeled TNBS-sensitized or nonsensitized lymphocytes to TNBS and saline control mice. Colon uptake was calculated normalized to bone marrow uptake in pelvis and corrected for background activity: (colon – background)/(bone marrow – background). Box plots of mean radioactivity uptake in 4 groups are shown (donor–acceptor). Overall comparison, P = 0.002; individual comparison between TNBS–TNBS group and 3 other groups, **P = 0.004 (statistically significant).
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FIGURE 2. Increased radioactivity on SPECT of mice with TNBS colitis mice transferred with TNBS-sensitized 111In-labeled lymphocytes. SPECT was performed 48 h after transfer of 111In-labeled TNBS-sensitized or nonsensitized lymphocytes to TNBS and saline control mice. Transverse slices from abdominal region at pelvic level are shown; amount of 111In uptake is color coded from low (black) to high (white). Four images are representative of 4 groups (donor–acceptor). (A) Colon uptake is low in NaCl–NaCl mouse. (B) Colon uptake is equivocal in TNBS–NaCl mouse. (C) Colon uptake is equivocal in NaCl–TNBS mouse. (D) Colon uptake (arrow) is manifest in TNBS–TNBS mouse.
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FIGURE 3. TNBS-sensitized lymphocytes exacerbate colitis. TNBS or saline control mice were transferred with TNBS-sensitized or nonsensitized 111In-labeled lymphocytes as indicated (donor–acceptor). Weight of the last 6 cm of colon was determined on sacrifice after SPECT. TNBS–TNBS mice had significantly higher colon weights than weights of mice in other 3 groups. Data represent mean ± SEM. Overall comparison, P = 0.0015; individual comparison between TNBS–TNBS group and 3 other groups, **P < 0.05 (statistically significant).
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FIGURE 4. TNBS-sensitized lymphocytes exacerbate colitis. Extent of mucosal inflammation was graded and mean total histologic scores per group (donor–acceptor) are shown. (A and B) NaCl–NaCl mouse (A) and TNBS–NaCl mouse (B) with normal colon architecture and small number of leukocytes in mucosa. (C) NaCl–TNBS mouse with inflammation (significantly less severe than in D), consisting of edema and influx of inflammatory cells, but no ulcerations and fibrosis. (D) TNBS–TNBS mouse with severe colitis characterized by edema, extensive influx of inflammatory cells, ulcerations, crypt loss, and fibrosis. (Hematoxylin–eosin, x33)
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FIGURE 5. Colon uptake ratio correlated with parameters of colitis. Mice with TNBS colitis were transferred with TNBS-sensitized or nonsensitized 111In-labeled lymphocytes. Each symbol represents 1 mouse. (A) Significant correlation between histology (x-axis) and CUR (y-axis) (P < 0.001). Correlation coefficient R2 = 0.933. (B) Significant correlation between colon weight (x-axis) and CUR (y-axis) (P < 0.001). Correlation coefficient R2 = 0.836.
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Copyright © 2004 by the Society of Nuclear Medicine.
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