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31 December 2015 Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy
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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′-(18F) 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 18F-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.

John A. Cieslak, Zita A. Sibenaller, Susan A. Walsh, Laura L. Boles Ponto, Juan Du, John J. Sunderland, and Joseph J. Cullen "Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy," Radiation Research 185(1), 31-38, (31 December 2015). https://doi.org/10.1667/RR14203.1
Received: 15 July 2015; Accepted: 1 October 2015; Published: 31 December 2015
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