Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy
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 pr...
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Published in | Radiation research Vol. 185; no. 1; pp. 31 - 38 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
The Radiation Research Society
01.01.2016
Radiation Research Society Allen Press Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0033-7587 1938-5404 |
DOI: | 10.1667/RR14203.1 |