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Updated: Apr 28, 2026
Ex vivo Live Imaging of Lung Metastasis and Their Microenvironment
Published on: February 3, 2016
Multimodality imaging of IL-18--binding protein-Fc therapy of experimental lung metastasis
Qizhen Cao1, Weibo Cai, Gang Niu
1The Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.
Purpose:
Interleukin (IL)-18 plays important roles in cancer progression and metastasis. The goal of this study is to identify cell lines that are most sensitive to stand alone IL-18-binding protein (IL-18bp)-Fc treatment, to study the pharmacokinetics and tumor targeting efficiency of IL-18bp-Fc, and to evaluate the efficacy of IL-18bp-Fc in treating breast cancer experimental lung metastasis by multimodality imaging.
Experimental Design:
Reverse transcription-PCR, ELISA, and other cell-based assays were done on murine 4T1, CT-26, and B16F10 cells. The most IL-18bp-Fc-sensitive 4T1 cells were stably transfected with firefly luciferase (fLuc) and injected i.v. into female BALB/C mice to establish the experimental lung metastasis model. Tumor targeting efficiency and pharmacokinetics of IL-18bp-Fc was assessed by (64)Cu-DOTA-IL-18bp-Fc positron emission tomography (PET) and biodistribution studies. Two groups of fLuc-4T1 experimental lung metastasis tumor-bearing mice were each given saline or IL-18bp-Fc (1 mg/kg) daily i.p. Bioluminescence imaging, (18)F-FDG PET, and computed tomography scans were done to evaluate the treatment efficacy. Ex vivo experiments were also carried out to validate the imaging results.
Results:
IL-18bp-Fc had high and specific accumulation in the fLuc-4T1 lung metastasis tumor as evidenced by both PET and biodistribution studies. Bioluminescence imaging, (18)F-FDG PET, and computed tomography scans all revealed that IL-18bp-Fc treatment was effective in inhibiting the lung metastasis tumor progression, validated by ex vivo examination of the lung.
Conclusions:
IL-18bp-Fc therapy can inhibit 4T1 breast cancer experimental lung metastasis. Noninvasive multimodality molecular imaging is a powerful tool for evaluating the tumor targeting efficiency/pharmacokinetics of the drug and effective monitoring of the therapeutic response.
Insights
Interleukin-18-binding protein-Fc (IL-18bp-Fc) effectively inhibited 4T1 breast cancer lung metastasis in mice. Multimodality imaging confirmed IL-18bp-Fc
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Interleukin-18 (IL-18) is implicated in cancer progression and metastasis.
- Targeting IL-18 signaling is a potential therapeutic strategy for cancer.
- IL-18-binding protein-Fc (IL-18bp-Fc) is an investigational therapeutic agent.
Purpose of the Study:
- To identify cancer cell lines sensitive to IL-18bp-Fc treatment.
- To assess the pharmacokinetics and tumor targeting of IL-18bp-Fc.
- To evaluate the efficacy of IL-18bp-Fc in treating experimental breast cancer lung metastasis using multimodality imaging.
Main Methods:
- Cell-based assays were performed on murine cell lines (4T1, CT-26, B16F10).
- 4T1 cells were used to establish a lung metastasis model in mice.
- Pharmacokinetics and tumor targeting were evaluated using (64)Cu-DOTA-IL-18bp-Fc PET and biodistribution.
- Treatment efficacy was assessed using bioluminescence imaging, (18)F-FDG PET, and CT scans.
Main Results:
- IL-18bp-Fc demonstrated high and specific accumulation in lung metastasis tumors.
- Multimodality imaging revealed that IL-18bp-Fc treatment effectively inhibited lung metastasis progression.
- Ex vivo experiments validated the imaging-based therapeutic response.
Conclusions:
- IL-18bp-Fc therapy is effective in inhibiting 4T1 breast cancer experimental lung metastasis.
- Noninvasive multimodality molecular imaging is a valuable tool for drug evaluation and therapeutic monitoring.
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