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Multimodality Molecular Imaging of Tumor Angiogenesis

¹ Molecular Imaging Program at Stanford, Department of Radiology, Biophysics, and Bio-X Program, School of Medicine, Stanford University, Stanford, California; and ² Department of Radiology and Medical Physics, School of Medicine and Public Health, University of Wisconsin–Madison, Madison, Wisconsin

Correspondence: For correspondence or reprints contact either of the following: Xiaoyuan Chen, Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, School of Medicine, Stanford University, 1201 Welch Rd., P095, Stanford, CA 94305-5484. E-mail: shawchen{at}stanford.edu Weibo Cai, Departments of Radiology and Medical Physics, School of Medicine and Public Health, University of Wisconsin–Madison, K4/628 Clinical Science Center, 600 Highland Ave., Madison, WI 53792-3252. E-mail: wcai{at}uwhealth.org

Molecular imaging is a key component of 21st-century cancer management. The vascular endothelial growth factor (VEGF)/VEGF receptor signaling pathway and integrin _vβ₃, a cell adhesion molecule, play pivotal roles in regulating tumor angiogenesis, the growth of new blood vessels. This review summarizes the current status of tumor angiogenesis imaging with SPECT, PET, molecular MRI, targeted ultrasound, and optical techniques. For integrin _vβ₃ imaging, only nanoparticle-based probes, which truly target the tumor vasculature rather than tumor cells because of poor extravasation, are discussed. Once improvements in the in vivo stability, tumor-targeting efficacy, and pharmacokinetics of tumor angiogenesis imaging probes are made, translation to clinical applications will be critical for the maximum benefit of these novel agents. The future of tumor angiogenesis imaging lies in multimodality and nanoparticle-based approaches, imaging of protein–protein interactions, and quantitative molecular imaging. Combinations of multiple modalities can yield complementary information and offer synergistic advantages over any modality alone. Nanoparticles, possessing multifunctionality and enormous flexibility, can allow for the integration of therapeutic components, targeting ligands, and multimodality imaging labels into one entity, termed "nanomedicine," for which the ideal target is tumor neovasculature. Quantitative imaging of tumor angiogenesis and protein–protein interactions that modulate angiogenesis will lead to more robust and effective monitoring of personalized molecular cancer therapy. Multidisciplinary approaches and cooperative efforts from many individuals, institutions, industries, and organizations are needed to quickly translate multimodality tumor angiogenesis imaging into multiple facets of cancer management. Not limited to cancer, these novel agents can also have broad applications for many other angiogenesis-related diseases.

Key Words: tumor angiogenesis • vascular endothelial growth factor • vascular endothelial growth factor receptor • integrin _vβ₃ • multimodality molecular imaging

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