title: Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy.
abstract: Pharmacological ascorbate (AscH(-)) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells compared with normal cells. Positron emission tomography (PET) with the thymidine analog 3'-deoxy-3'-((18)F) fluorothymidine (FLT) enables noninvasive imaging and quantification of the proliferation fraction of tumors. We hypothesized that the rate of tumor proliferation determined by FLT-PET imaging, would be inversely proportional to tumor susceptibility to pharmacological AscH(-)-based treatments. Indeed, there was decreased FLT uptake in human pancreatic cancer cells treated with AscH(-) in vitro, and this effect was abrogated by co-treatment with catalase. In separate experiments, cells were treated with AscH(-), ionizing radiation or a combination of both. These studies demonstrated that combined AscH(-) and radiation treatment resulted in a significant decrease in FLT uptake that directly correlated with decreased clonogenic survival. MicroPET (18)F-FLT scans of mice with pre-established tumors demonstrated that AscH(-) treatment induced radiosensitization compared to radiation treatment alone. These data support testing of pharmacological ascorbate as a radiosensitizer in pancreatic cancer as well as the use of FLT-PET to monitor response to therapy.
authors.affiliation: a  Free Radical and Radiation Biology Program, Department of Radiation Oncology; Departments of.|b  Surgery;
authors.forename: John A
authors.initials: JA
authors.lastname: Cieslak
authors.affiliation: a  Free Radical and Radiation Biology Program, Department of Radiation Oncology; Departments of.
authors.forename: Zita A
authors.initials: ZA
authors.lastname: Sibenaller
authors.affiliation: a  Free Radical and Radiation Biology Program, Department of Radiation Oncology; Departments of.|d  Small Animal Imaging Core, University of Iowa Carver College of Medicine, Iowa City, Iowa;
authors.forename: Susan A
authors.initials: SA
authors.lastname: Walsh
authors.affiliation: c  Radiology and.|d  Small Animal Imaging Core, University of Iowa Carver College of Medicine, Iowa City, Iowa;
authors.forename: Laura L Boles
authors.initials: LL
authors.lastname: Ponto
authors.affiliation: a  Free Radical and Radiation Biology Program, Department of Radiation Oncology; Departments of.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: c  Radiology and.
authors.forename: John J
authors.initials: JJ
authors.lastname: Sunderland
authors.affiliation: a  Free Radical and Radiation Biology Program, Department of Radiation Oncology; Departments of.|b  Surgery;|e  Holden Comprehensive Cancer Center, Iowa City, Iowa; and.|f  Iowa City Veterans Affairs Medical Center, Iowa City, Iowa.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Cullen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy / Q000379:methods; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D007553:Isotope Labeling; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy*; D049268:Positron-Emission Tomography / Q000379:methods*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011879:Radiotherapy Dosage; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; C002854:alovudine; D001205:Ascorbic Acid