Positron Emission Tomography Imaging of Cell Proliferation in Oncology

Kenny, Liz; Aboagye, Eric O.; Price, Patricia M

doi:10.1016/j.clon.2003.10.009

Cited by 28 publications

(15 citation statements)

References 63 publications

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“…Thus, increase in nucleoside uptake after thymidylate synthase inhibition may be a general phenomenon that could be exploited to assess pharmacodynamics of thymidylate synthase inhibitors. Furthermore, it is not cell type dependent as the effects are seen in mouse and human cells, including RIF-1, HT29, and KB cells (11,24 (29). Hence, we assessed the feasibility of using this radiotracer for imaging thymidylate synthase inhibition.…”

Section: Discussionmentioning

confidence: 99%

Redistribution of Nucleoside Transporters to the Cell Membrane Provides a Novel Approach for Imaging Thymidylate Synthase Inhibition by Positron Emission Tomography

et al. 2006

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Thymidylate synthase (EC 2.1.1.45) is a key enzyme for the de novo synthesis of DNA and as such a target for anticancer drug development. There is a need to develop noninvasive methods for assessing thymidylate synthase inhibition in tumors. The aim of this study was to assess the potential of 3 ¶-deoxy-3 ¶-[18 F]fluorothymidine ([ 18 F]FLT) positron emission tomography (PET) for early measurement of thymidylate synthase inhibition and to elucidate the cellular mechanisms involved. Radiation-induced fibrosarcoma-1 tumor-bearing mice were injected with a single i.p. dose of the thymidylate synthase inhibitor 5-fluorouracil (5-FU; 165 mg/kg) and imaged by [18 F]FLT-PET at 1 to 2 hours after treatment. Deoxyuridine, thymidine kinase 1 (cytoplasmic thymidine kinase; EC2.7.1.21), and ATP levels in excised tumors were measured. Cellular assays for membrane transport were also done. There was a 1.8-fold increase in the 60-minute [18 F]FLT tumor/heart radioactivity ratio in drug-treated mice compared with vehicle controls (P = 0.0016). Plasma and tumor deoxyuridine levels increased significantly but thymidine kinase and ATP levels were unchanged. Whole-cell assays implicated a (low level) functional role for the type-1 equilibrative nucleoside transporter (ENT). There was an increase in type-1 ENT-binding sites per cell from 49,110 in untreated cells to 73,142 (P = 0.03) in cells treated with 10 Mg/mL 5-FU for 2 hours, without a change in transporter affinity (P = 0.41). We conclude that [18 F]FLT-PET can be used to measure thymidylate synthase inhibition as early as 1 to 2 hours after treatment with 5-FU by a mechanism involving redistribution of nucleoside transporters to the plasma membrane. (Cancer Res 2006; 66(17): 8558-64)

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Section: Discussionmentioning

confidence: 99%

Redistribution of Nucleoside Transporters to the Cell Membrane Provides a Novel Approach for Imaging Thymidylate Synthase Inhibition by Positron Emission Tomography

et al. 2006

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“…Currently, there are multitudes of imaging agents available for imaging various cancer-related targets at a basic research level (as well as some for clinical applications). Examples include agents for angiogenesis (25,43,68), hypoxia (230,286), proliferation (201,308), tumor metabolism (338), apoptosis (139,141), and metastasis (131,300,322). The scope of this review does not allow for a detailed description of how molecular imaging agents can be used to visualize each of these processes; however, please refer to the reviews referenced above along with the following reviews (6,121,430) for further details.…”

Section: A Oncologymentioning

confidence: 99%

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

James

Gambhir

2012

Physiological Reviews

967

954

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Molecular imaging is revolutionizing the way we study the inner workings of the human body, diagnose diseases, approach drug design, and assess therapies. The field as a whole is making possible the visualization of complex biochemical processes involved in normal physiology and disease states, in real time, in living cells, tissues, and intact subjects. In this review, we focus specifically on molecular imaging of intact living subjects. We provide a basic primer for those who are new to molecular imaging, and a resource for those involved in the field. We begin by describing classical molecular imaging techniques together with their key strengths and limitations, after which we introduce some of the latest emerging imaging modalities. We provide an overview of the main classes of molecular imaging agents (i.e., small molecules, peptides, aptamers, engineered proteins, and nanoparticles) and cite examples of how molecular imaging is being applied in oncology, neuroscience, cardiology, gene therapy, cell tracking, and theranostics (therapy combined with diagnostics). A step-by-step guide to answering biological and/or clinical questions using the tools of molecular imaging is also provided. We conclude by discussing the grand challenges of the field, its future directions, and enormous potential for further impacting how we approach research and medicine.

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“…Information additional and complementary to 18 F-FDG may be obtained using the thymidine analog 39-deoxy-39- 18 F-fluorothymidine ( 18 F-FLT) to study tumor cell proliferation. Thymidine incorporation into DNA is considered a gold standard measure of proliferation, and 18 F-FLT uptake closely reflects tumor cell proliferation (10). 18 F-FLT PET/CT could therefore be a valuable marker of tumor response to antiproliferative treatments including RT.…”

mentioning

confidence: 99%

Differential ¹⁸F-FDG and ¹⁸F-FLT Uptake on Serial PET/CT Imaging Before and During Definitive Chemoradiation for Non–Small Cell Lung Cancer

et al. 2014

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Positron Emission Tomography Imaging of Cell Proliferation in Oncology

Cited by 28 publications

References 63 publications

Redistribution of Nucleoside Transporters to the Cell Membrane Provides a Novel Approach for Imaging Thymidylate Synthase Inhibition by Positron Emission Tomography

Redistribution of Nucleoside Transporters to the Cell Membrane Provides a Novel Approach for Imaging Thymidylate Synthase Inhibition by Positron Emission Tomography

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

Differential ¹⁸F-FDG and ¹⁸F-FLT Uptake on Serial PET/CT Imaging Before and During Definitive Chemoradiation for Non–Small Cell Lung Cancer

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Positron Emission Tomography Imaging of Cell Proliferation in Oncology

Cited by 28 publications

References 63 publications

Redistribution of Nucleoside Transporters to the Cell Membrane Provides a Novel Approach for Imaging Thymidylate Synthase Inhibition by Positron Emission Tomography

Redistribution of Nucleoside Transporters to the Cell Membrane Provides a Novel Approach for Imaging Thymidylate Synthase Inhibition by Positron Emission Tomography

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

Differential 18F-FDG and 18F-FLT Uptake on Serial PET/CT Imaging Before and During Definitive Chemoradiation for Non–Small Cell Lung Cancer

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Product

Resources

About

Differential ¹⁸F-FDG and ¹⁸F-FLT Uptake on Serial PET/CT Imaging Before and During Definitive Chemoradiation for Non–Small Cell Lung Cancer