Imaging proliferation in vivo with [F-18]FLT and positron emission tomography

Shields, Anthony F.; Grierson, John R.; Dohmen, Bernhard M.; Machulla, H.-J.; Stayanoff, Joseph C.; Lawhorn-Crews, Jawana M.; Obradovich, Joyce E.; Muzik, Otto; Mangner, Thomas J.

doi:10.1038/3337

Cited by 1,105 publications

(768 citation statements)

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“…Thus, a noninvasive method to evaluate tumor proliferation is necessary. 18 F-fluorothymidine (FLT) PET which reflects thymidine kinase 1 (TK1) activity is one of the noninvasive methods of detecting tumor proliferation [14][15][16][17][18]. TK1 activity is extremely sensitive to ionizing radiation, and the changes in FLT uptake level directly reflect the biological effect of radiation therapy [19,20].…”

Section: Introductionmentioning

confidence: 99%

Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

et al. 2013

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Objective Although radiotherapy is an important treatment strategy for head and neck cancers, it induces tumor repopulation which adversely affects therapeutic outcome. In this regard, fractionated radiotherapy is widely applied to prevent tumor repopulation. Evaluation of tumor proliferative activity using 18 F-fluorothymidine (FLT), a noninvasive marker of tumor proliferation, may be useful for determining the optimal timing of and dose in the repetitive irradiation. Thus, to assess the potentials of FLT, we evaluated the sequential changes in intratumoral proliferative activity in head and neck cancer xenografts (FaDu) using FLT. MethodsFaDu tumor xenografts were established in nude mice and assigned to control and two radiation-treated groups (10 and 20 Gy). Tumor volume was measured daily. 3 H-FLT was injected intravenously 2 hrs before sacrifice. Mice were sacrificed 6, 24, 48 hrs, and 7 days after the radiation treatment. Intratumoral 3 H-FLT level was visually and quantitatively assessed by autoradiography. Ki-67 immunohistochemistry (IHC) was performed. ResultsIn radiation-treated mice, the tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. In the visual assessment, intratumoral 3 H-FLT level diffusely decreased 6 hrs after the radiation treatment and then gradually increased with time, whereas no apparent changes were observed in Ki-67 IHC. Six hours after the radiation treatment at 10 and 20 Gy, the intratumoral 3 H-FLT level markedly decreased to 45 and 40% of the control, respectively (P < 0.0001, vs control), and 4 then gradually increased with time. In each radiation-treated group, the 3 H-FLT levels at 48 hrs and on day 7 were significantly higher than that at 6 hrs. The Intratumoral 3 H-FLT levels in both treated groups were 68 and 60% at 24 hrs (P < 0.001), 71 and 77% at 48 hrs (P < 0.001), and 83and 81% on day 7 (P = NS) compared with the control group.Conclusion Intratumoral FLT uptake level markedly decreased at 6 hrs and then gradually increased with time. Sequential evaluation of intratumoral proliferative activity using FLT can be beneficial for determining the optimal timing of and dose in repetitive irradiation of head and neck cancer.

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Section: Introductionmentioning

confidence: 99%

Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

et al. 2013

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“…61 This problem spurred the development of FLT, an 18 F-labeled, nonmetabolized thymidine analogue that has become the most extensively studied radiotracer for imaging tumor proliferation. 62,63 After intravenous injection, FLT enters the cell by facilitated diffusion through nucleoside transporters and is trapped in the cytosol through phosphorylation. 64 Because FLT lacks a hydroxyl group at the 3 0 position, it is not incorporated into DNA, and its accumulation serves as a measure of cellular proliferation.…”

Section: Imaging Proliferationmentioning

confidence: 99%

PET/CT imaging in cancer: Current applications and future directions

Farwell

Pryma

Mankoff

2014

Cancer

191

120

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Positron emission tomography (PET) is a radiotracer imaging method that yields quantitative images of regional in vivo biology and biochemistry. PET, now used in conjunction with computed tomography (CT) in PET/CT devices, has had its greatest impact to date on cancer and is now an important part of oncologic clinical practice and translational cancer research. In this review of current applications and future directions for PET/CT in cancer, the authors first highlight the basic principles of PET followed by a discussion of the biochemistry and current clinical applications of the most commonly used PET imaging agent, 18 F-fluorodeoxyglucose (FDG). Then, emerging methods for PET imaging of other biologic processes relevant to cancer are reviewed, including cellular proliferation, tumor hypoxia, apoptosis, amino acid and cell membrane metabolism, and imaging of tumor receptors and other tumor-specific gene products. The focus of the review is on methods in current clinical practice as well as those that have been translated to patients and are currently in clinical trials. Cancer 2014;120:3433-45.

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“…A series of PET probes that were subsequently developed to address these limitations include the F-18-labeled analogs 3′-deoxy-3′-18 F-fluorothymidine ( 18 F-FLT) and 1-(2′-deoxy-2′-18 F-fluoro-beta-D-arabinofuranosyl)thymine ( 18 F-FMAU) [47]. 18 F-FLT is taken up by cells and phosphorylated by TK1 with subsequent trapping within the cell [48]. Unlike thymidine, 18 F-FLT lacks the 3'-hydroxyl group and cannot be incorporated into DNA; however, being a substrate for TK1, it is still trapped in the cell as 18 F-FLT-monophosphate and can serve as an indirect measure of cell proliferation.…”

Section: Thymidine Analogsmentioning

confidence: 99%

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

Zhu

Shim

2011

Nucl Med Mol Imaging

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Molecular imaging is one of the fastest growing areas of medical imaging. Positron emission tomography (PET) has been widely used in the clinical management of patients with cancer. Nuclear imaging provides biological information at the cellular, subcellular, and molecular level in living subjects with noninvasive procedures. In particular, PET imaging takes advantage of traditional diagnostic imaging techniques and introduces positron-emitting probes to determine the expression of indicative molecular targets at different stages of cancer. 18 F-fluorodeoxyglucose ( 18 F-FDG), the only FDA approved oncological PET tracer, has been widely utilized in cancer diagnosis, staging, restaging, and even monitoring response to therapy; however, 18 F-FDG is not a tumor-specific PET tracer. Over the last decade, many promising tumor-specific PET tracers have been developed and evaluated in preclinical and clinical studies. This review provides an overview of the current non-18 F-FDG PET tracers in oncology that have been developed based on tumor characteristics such as increased metabolism, hyperproliferation, angiogenesis, hypoxia, apoptosis, and tumor-specific antigens and surface receptors.

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Imaging proliferation in vivo with [F-18]FLT and positron emission tomography

Cited by 1,105 publications

References 10 publications

Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67

PET/CT imaging in cancer: Current applications and future directions

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

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