This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cao, Q. Articles by Chen, X. Search for Related Content PubMed PubMed Citation Articles by Cao, Q. Articles by Chen, X.

Multimodality Imaging of IL-18–Binding Protein-Fc Therapy of Experimental Lung Metastasis

Authors' Affiliations: ¹ The Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University School of Medicine, Stanford, California and ² Departments of Radiology and Medical Physics, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, Wisconsin

Requests for reprints: Xiaoyuan Chen, The Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Road, P095, Stanford, CA 94305-5484. Phone: 650-725-0950; Fax: 650-736-7925; E-mail: shawchen{at}stanford.edu.

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 ⁶⁴Cu-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, ¹⁸F-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, ¹⁸F-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.