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Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development

Authors' Affiliations: ¹ Cancer Imaging Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, Maryland; ² Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; ³ Memorial Sloan-Kettering Cancer Center, New York, New York; ⁴ Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, St. Louis, Missouri; ⁵ Department of Orthopaedic Surgery, University of Minnesota and Orthopaedic Surgery Service, Fairview University Medical Center, Minneapolis, Minnesota; ⁶ Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; ⁷ Baylor Charles A. Sammons Cancer Center, Dallas, Texas; ⁸ CCS Associates, Mountain View, California; ⁹ Division of Nuclear Medicine, Department of Radiology, University of Washington, Seattle, Washington; and ¹⁰ Section of Hematology/Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois

Requests for reprints: Gary J. Kelloff, Cancer Imaging Program, Division of Cancer Treatment and Diagnostics, National Cancer Institute, NIH, EPN 6130 Executive Boulevard, Suite 6058, Bethesda, MD 20892. Fax: 301-480-3507; E-mail: kelloffg{at}mail.nih.gov.

2-[¹⁸F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) assesses a fundamental property of neoplasia, the Warburg effect. This molecular imaging technique offers a complementary approach to anatomic imaging that is more sensitive and specific in certain cancers. FDG-PET has been widely applied in oncology primarily as a staging and restaging tool that can guide patient care. However, because it accurately detects recurrent or residual disease, FDG-PET also has significant potential for assessing therapy response. In this regard, it can improve patient management by identifying responders early, before tumor size is reduced; nonresponders could discontinue futile therapy. Moreover, a reduction in the FDG-PET signal within days or weeks of initiating therapy (e.g., in lymphoma, non–small cell lung, and esophageal cancer) significantly correlates with prolonged survival and other clinical end points now used in drug approvals. These findings suggest that FDG-PET could facilitate drug development as an early surrogate of clinical benefit. This article reviews the scientific basis of FDG-PET and its development and application as a valuable oncology imaging tool. Its potential to facilitate drug development in seven oncologic settings (lung, lymphoma, breast, prostate, sarcoma, colorectal, and ovary) is addressed. Recommendations include initial validation against approved therapies, retrospective analyses to define the magnitude of change indicative of response, further prospective validation as a surrogate of clinical benefit, and application as a phase II/III trial end point to accelerate evaluation and approval of novel regimens and therapies.

Key Words: FDG-PET • molecular imaging • oncology • drug development

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