Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy

John A Cieslak; Zita A Sibenaller; Susan A Walsh; Laura L Boles Ponto; Juan Du; John J Sunderland; Joseph J Cullen

doi:10.1667/RR14203.1

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Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy

Journal article

Peer reviewed

Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy

John A Cieslak, Zita A Sibenaller, Susan A Walsh, Laura L Boles Ponto, Juan Du, John J Sunderland and Joseph J Cullen

Radiation research, Vol.185(1), pp.31-38

01/2016

DOI: 10.1667/RR14203.1

PMCID: PMC4720529

PMID: 26720803

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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'-((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.

Radiotherapy Dosage

Chemoradiotherapy - methods

Pancreatic Neoplasms - metabolism

Radiopharmaceuticals - pharmacokinetics

Humans

Ascorbic Acid - administration & dosage

Metabolic Clearance Rate

Treatment Outcome

Antineoplastic Agents - administration & dosage

Drug Monitoring - methods

Positron-Emission Tomography - methods

Dideoxynucleosides - pharmacokinetics

Animals

Radiation-Sensitizing Agents - administration & dosage

Mice, Nude

Cell Line, Tumor

Isotope Labeling

Cell Proliferation - drug effects

Mice

Pancreatic Neoplasms - diagnostic imaging

Cell Proliferation - radiation effects

Pancreatic Neoplasms - therapy

Details

Title: Subtitle: Fluorine-18-Labeled Thymidine Positron Emission Tomography (FLT-PET) as an Index of Cell Proliferation after Pharmacological Ascorbate-Based Therapy
Creators: John A Cieslak - b Surgery
Zita A Sibenaller - a Free Radical and Radiation Biology Program, Department of Radiation Oncology; Departments of
Susan A Walsh - d Small Animal Imaging Core, University of Iowa Carver College of Medicine, Iowa City, Iowa
Laura L Boles Ponto - d Small Animal Imaging Core, University of Iowa Carver College of Medicine, Iowa City, Iowa
Juan Du - a Free Radical and Radiation Biology Program, Department of Radiation Oncology; Departments of
John J Sunderland - c Radiology and
Joseph J Cullen - f Iowa City Veterans Affairs Medical Center, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Radiation research, Vol.185(1), pp.31-38
DOI: 10.1667/RR14203.1
PMID: 26720803
PMCID: PMC4720529
NLM abbreviation: Radiat Res
ISSN: 0033-7587
eISSN: 1938-5404
Publisher: United States
Grant note: R01CA169046 / NCI NIH HHS T32 CA078586 / NCI NIH HHS I01 BX001318 / BLRD VA CA184051 / NCI NIH HHS R01 CA184051 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA169046 / NCI NIH HHS CA078586 / NCI NIH HHS
Language: English
Date published: 01/2016
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Physics and Astronomy; Radiation Oncology
Record Identifier: 9984046917602771

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