Conjugation with 111In-DTPA-Poly(Ethylene Glycol) Improves Imaging of Anti-EGF Receptor Antibody C225

Conjugation with ¹¹¹In-DTPA-Poly(Ethylene Glycol) Improves Imaging of Anti-EGF Receptor Antibody C225

Xiaoxia Wen, Qing-Ping Wu, Shi Ke, Lee Ellis, Chusilp Charnsangavej, Abraham S. Delpassand, Sidney Wallace and Chun Li

Division of Diagnostic Imaging and Department of Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas

View larger version (22K):

[in a new window]

FIGURE 1. Sequential ${gamma}$ -images of mouse injected with ¹¹¹In-DTPA-C225. Mouse, which had A431 tumors (arrowheads) in chest and right hind limb, was administered 10 µg ¹¹¹In-DTPA-C225 through tail vein. Whole-body images were obtained 5 min and 6, 24, and 48 h after injection. Radioactivity was predominantly in liver (arrow) at 24 and 48 h after injection. Anterior views of mouse placed prone on camera’s pinhole collimator, with head pointing to top.

View larger version (30K):

[in a new window]

FIGURE 2. Sequential ${gamma}$ -images of mouse injected intravenously with 10 µg 1:10 ¹¹¹In-DTPA-PEG-C225. Tumors are seen in 24-h postinjection image (arrowheads). Radioactivity in liver (arrow) is markedly lower than in images in Figure 1. Anterior views of mouse placed prone on camera’s pinhole collimator, with head pointing to top.

View larger version (33K):

[in a new window]

FIGURE 3. Sequential ${gamma}$ -images of mouse injected intravenously with 10 µg 1:30 ¹¹¹In-DTPA-PEG-C225. Radioactivity in liver (arrow) is markedly lower than in images in Figure 1. Tumor (arrowheads) in hind limb is clearly seen at 6, 24, and 48 h after injection. Anterior views of mouse placed prone on camera’s pinhole collimator, with head pointing to top.

View larger version (20K):

[in a new window]

FIGURE 4. Quantification of tumor-to-liver ratios from sequential ${gamma}$ -images of ¹¹¹In-labeled C225 conjugates. Data are expressed as ratios of tumor-to-liver radioactivity per pixel and presented as mean ± SEM (n = 3). Tumor-to-liver ratios for both PEG-modified C225 conjugates are significantly higher than ratio for C225 without PEG at each time point (P < 0.05).

View larger version (27K):

[in a new window]

FIGURE 5. Representative ${gamma}$ -images of mice without (A) and with (B) C225 pretreatment 6 and 24 h after radiotracer injection. Mice with A431 tumors were injected with 1:30 ¹¹¹In-DTPA-PEG-C225 alone or 20 h after injection of unlabeled C225 at dose of 1 mg per mouse. Pairs of mice used in imaging study were matched for size of tumors. Tumors (arrowheads) in mouse injected with only 1:30 ¹¹¹In-DTPA-PEG-C225 are clearly visualized (A), whereas tumors (arrows) in mouse pretreated with C225 are hardly seen (B). Anterior views of mouse placed prone on camera’s pinhole collimator, with head pointing to top.

View larger version (38K):

[in a new window]

FIGURE 6. ${gamma}$ -Scintigrams of human tumor xenografts expressing different levels of EGFR. Mice with A431 (A), MDA-MB-468 (B), or MDA-MB-435 tumors (C) received 10 µg per mouse of 1:30 ¹¹¹In-DTPA-PEG-C225 intravenously. Images were acquired 24 h after radioligand injection. A431 (A) and MDA-MB-468 tumors (B; arrowheads) are more readily visualized than MDA-MB-435 tumors (C; arrowheads). Anterior views of mice placed prone on camera’s pinhole collimator, with heads pointing to top.

View larger version (21K):

[in a new window]

FIGURE 7. Tumor-to-blood ratios for mice bearing human A431, MDA-MB-468, or MDA-MB-435 xenografts with or without C225 pretreatment. Mice were injected intravenously with 10 µg per mouse of 1:30 ¹¹¹In-DTPA-PEG-C225 alone or 20 h after pretreatment with native C225 and killed 48 h later; tissues were removed for radioactivity quantification. Data, expressed as ratios of ID/g in tumor to ID/g in blood, are presented as mean ± SEM (n = 3). Tumor-to-blood ratios for A431 and MDA-MB-468 tumors are significantly higher (P = 0.009 and P < 0.001, respectively) than ratio for MDA-MB-435 tumors. Pretreatment with C225 resulted in significant decreases of tumor-to-blood ratios for A431 and MDA-MB-468 tumors (P = 0.04 and P < 0.001, respectively) but not for MDA-MB-435 tumors (P = 0.3).