title: The progress and promise of molecular imaging probes in oncologic drug development.
abstract: As addressed by the recent Food and Drug Administration Critical Path Initiative, tools are urgently needed to increase the speed, efficiency, and cost-effectiveness of drug development for cancer and other diseases. Molecular imaging probes developed based on recent scientific advances have great potential as oncologic drug development tools. Basic science studies using molecular imaging probes can help to identify and characterize disease-specific targets for oncologic drug therapy. Imaging end points, based on these disease-specific biomarkers, hold great promise to better define, stratify, and enrich study groups and to provide direct biological measures of response. Imaging-based biomarkers also have promise for speeding drug evaluation by supplementing or replacing preclinical and clinical pharmacokinetic and pharmacodynamic evaluations, including target interaction and modulation. Such analyses may be particularly valuable in early comparative studies among candidates designed to interact with the same molecular target. Finally, as response biomarkers, imaging end points that characterize tumor vitality, growth, or apoptosis can also serve as early surrogates of therapy success. This article outlines the scientific basis of oncology imaging probes and presents examples of probes that could facilitate progress. The current regulatory opportunities for new and existing probe development and testing are also reviewed, with a focus on recent Food and Drug Administration guidance to facilitate early clinical development of promising probes.
authors.affiliation: Cancer Imaging Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD 20892, USA. kelloffg@mail.nih.gov
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Kelloff
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Krohn
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: David A
authors.initials: DA
authors.lastname: Mankoff
authors.forename: John M
authors.initials: JM
authors.lastname: Hoffman
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Link
authors.forename: Kathryn Z
authors.initials: KZ
authors.lastname: Guyton
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Sigman
authors.forename: James L
authors.initials: JL
authors.lastname: Tatum
authors.forename: George Q
authors.initials: GQ
authors.lastname: Mills
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Sullivan
authors.forename: Janet
authors.initials: J
authors.lastname: Woodcock
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003952:Diagnostic Imaging / Q000379:methods* / Q000639:trends; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D019275:Radiopharmaceuticals; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals