Article Figures & Data
Figures
- FIGURE 1.
Small-animal PET imaging in a bilateral ovarian tumor model. Representative longitudinal transverse and coronal PET images of 89Zr-DFO-mAb-B43.13 (7–10 MBq injected via tail vein) in athymic nude mice bearing bilateral subcutaneous CA125-positive OVCAR3 tumors xenografted on the left shoulder (white arrows) and CA125-negative SKOV3 tumors on the right shoulder (orange arrows).
- FIGURE 2.
CA125-targeted PET imaging with 89Zr-DFO-mAb-B43.13. Serial PET images of an athymic nude mouse bearing a CA125-positive OVCAR3 xenograft after the administration of 89Zr-DFO-mAb-B43.13 via tail vein injection (10.2–12.0 MBq). Coronal planar images intersect the middle of the tumor. L = liver; T = tumor.
- FIGURE 3.
Acute biodistribution of 89Zr-DFO-mAb-B43.13 in tumor-bearing mice. Biodistribution data from athymic nude mice (n = 4 per time point) bearing CA125-positive OVCAR3 xenografts after the administration of 89Zr-DFO-mAb-B43.13 via tail vein injection (0.55–0.74 MBq, 4–6 μg). *P = 0.0093. %ID/g values are provided in Supplemental Table 1.
- FIGURE 4.
Visualization of LNs with 89Zr-DFO-mAb-B43.13. (A) Coronal PET images (120 h after injection) of 3 OVCAR3 tumor–bearing mice demonstrating uptake of the radioimmufnoconjugate in the ipsilateral chain of LNs. (B; left) PET image obtained 120 h after injection of 89Zr-DFO-mAb-B43.13 in an OVCAR3 xenograft–bearing mouse revealing a bilobed tumor with a radioactive focal point indicative of LN involvement. (B; right) Maximum-intensity projection (MIP) from ex vivo PET imaging of the harvested tumor and axillary and brachial LNs from the ipsilateral and contralateral chains. (C) Biodistribution of 89Zr-DFO-mAb-B43.13 and 89Zr-DFO-IgG in OVCAR3 xenograft–bearing mice (n = 4 per group) comparing activity concentrations of the 2 radioimmunoconjugates in the tumor, relevant LNs, and liver. ALN = axillary LNs; BLN = brachial LNs; C-ALN = contralateral axillary LN; C-BLN = contralateral brachial LN; I-ALN = ipsilateral axillary LN; I-BLN = ipsilateral brachial LN; L = liver; SMLN = submandibular LNs; T = tumor. *P < 0.05.
- FIGURE 5.
PET images of 89Zr-DFO-mAb-B43.13 demonstrating the progression of LN metastasis. (A) Coronal (top) and maximum-intensity projection (MIP; bottom) PET image obtained 72 h after the administration of 89Zr-DFO-mAb-B43.13 to a mouse 8 wk after implantation of an OVCAR3 xenograft on the right shoulder. (B) Coronal (top) and MIP (bottom) PET images obtained 72 h after the administration of 89Zr-DFO-mAb-B43.13 to the same mouse 11 wk after the implantation of the OVCAR3 xenograft on the right shoulder. (C) PET/CT image obtained 120 h after the administration of 89Zr-DFO-mAb-B43.13 to the same mouse 11 wk after the implantation of the OVCAR3 xenograft on the right shoulder. ALN = axillary LNs; BLN = brachial LN; L = liver; max = maximum; min = minimum; p.i. = after injection; SMLN = submandibular LN; T = tumor.
- FIGURE 6.
Ex vivo analysis of OVCAR3 tumors after PET imaging. (A) Hematoxylin and eosin–stained OVCAR3 tumor section outlining the architecture of the tumor. (B) Digital autoradiograph demonstrating the distribution of 89Zr-DFO-mAb-B43.13 within the tumor. (C) Hoechst 33342 dye (blue) fluorescence map of the tumor vasculature. (D) Overlay of the digital autoradiograph with the Hoechst dye fluorescence map illustrating the role of vasculature in the heterogeneous and limited distribution of 89Zr-DFO-mAb-B43.13 in the tumor. Bottom row contains higher-magnification images of the corresponding sections A–D from the boxed area shown in 6B.
- FIGURE 7.
Histopathologic analyses of the primary tumor and the ipsilateral submandibular and axillary LN tissues. (Central image) Coronal PET image showing the primary OVCAR3 tumor and the ipsilateral submandibular and axillary LNs in a mouse (Fig. 5B) injected with 89Zr-DFO-mAb-B43.13. (A–C) ×20 and ×10 magnification of tissue sections from the ipsilateral submandibular LN (A), the ipsilateral axillary LN (B), and the primary tumor stained with hematoxylin and eosin (H&E; top) and immunohistochemistry (IHC; bottom) for CA125 (C). In IHC images, the lymphocytes appear blue, whereas the metastatic ovarian cancer cells appear dark brown, indicating positive staining for the expression of CA125 along the circumference of ovarian cancer (OvCa) cells.
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