title: Measuring tumor pharmacodynamic response using PET proliferation probes: the case for 2-[(11)C]-thymidine.
abstract: [(18)F]-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) is becoming accepted as a diagnostic tool for cancer, but the potential uses of PET in oncology extend beyond the imaging of glucose metabolism. The development of a PET proliferation probe would be a useful pharmacodynamic tool. [(11)C]-thymidine PET has been assessed in man as a specific measure of tumor proliferation. Uptake of [(11)C]-thymidine is related to DNA synthesis and, in human tumors, correlates with proliferation. When compared with (18)F-FDG, it has been shown to be a more sensitive discriminator of early clinical tumor response. 2-[(11)C]-thymidine PET scanning of patients enrolled in early phase clinical trials is feasible and should support future drug development. Although recent research is moving away from the validation of thymidine towards thymidine analogues radiolabeled with (18)F, the better specificity of thymidine for DNA should be the rationale for its continued development and application as a PET probe. This review describes the historical development, application and current research status of [(11)C]-thymidine PET, and aims to highlight the need for its continuing development as a marker of tumor proliferation.
authors.affiliation: Department of Radiotherapy, St. Bartholomews' Hospital, West Smithfield, London EC1A 7BE, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Wells
authors.forename: Catharine
authors.initials: C
authors.lastname: West
authors.forename: Terry
authors.initials: T
authors.lastname: Jones
authors.forename: Adrian
authors.initials: A
authors.lastname: Harris
authors.forename: Pat
authors.initials: P
authors.lastname: Price
mesh_terms: D002250:Carbon Radioisotopes; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D015342:DNA Probes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D013936:Thymidine / Q000737:chemistry
chemical_list: D002250:Carbon Radioisotopes; D015342:DNA Probes; D019788:Fluorodeoxyglucose F18; D013936:Thymidine