JNM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rasey, J. S.
Right arrow Articles by Schwartz, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rasey, J. S.
Right arrow Articles by Schwartz, J. L.
Journal of Nuclear Medicine Vol. 43 No. 9 1210-1217
© 2002 by Society of Nuclear Medicine

Basic Science Investigations

Validation of FLT Uptake as a Measure of Thymidine Kinase-1 Activity in A549 Carcinoma Cells

Janet S. Rasey, PhD1, John R. Grierson, PhD2, Linda W. Wiens, BS1, Pamella D. Kolb, BS1 and Jeffrey L. Schwartz, PhD1

1 Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington
2 Department of Radiology, University of Washington School of Medicine, Seattle, Washington

The thymidine analog 18F-3'-deoxy-3' -fluorothymidine (FLT) is being used clinically for PET imaging of tumor proliferation. Appropriate use of this tracer requires validating the mechanisms by which it accumulates in dividing cells. We tested the accuracy with which FLT uptake predicted the activity of cytosolic thymidine kinase-1 (TK1), an enzyme that is upregulated before and during DNA synthesis. Methods: Cultured A549 human lung carcinoma cells were manipulated to a range of proliferation rates from actively dividing to growth arrested. Uptake of radiolabeled FLT was compared with cell cycle activity, which was expressed as the percentage of cells in S phase, and with activity of cytosolic TK1. We also compared uptake of FLT and deoxyglucose. We genetically manipulated A549 cells by transfecting them with human papillomavirus type 16 E6 (designated A549-E6) to abrogate function of the tumor suppressor gene, p53. Although radiation typically inhibits progression of mammalian cells through the cell cycle, abrogation of p53 function eliminates this inhibition. We then compared FLT uptake with the percentage of cells in S phase and TK1 activity in irradiated A549-E6 cells and in irradiated control cells having normal p53 function and the expected radiation-induced growth delay. Results: A549 cells with only 3%–5% cells in S phase took up little FLT and had low levels of TK1 activity. When cells were stimulated to grow by being placed into fresh medium, we observed a strong correlation between increased FLT uptake and increased TK1 activity. As expected, FLT uptake varied much more as a function of growth than did uptake of deoxyglucose. Nonproliferating A549 cells did not enter the cell cycle if they were irradiated before being placed into fresh medium, and they did not accumulate FLT or show elevated TK1 activity. In contrast, radiation did not inhibit the cell cycle progression of A549-E6 cells. When subcultured, they began to grow and showed increased uptake of FLT commensurate with greater TK1 activity. Conclusion: In cultured A549 cells FLT uptake is positively correlated with cell growth and TK1 activity. Inhibition of cell cycle progression prevents FLT uptake and increased TK1 activity. These results suggest that FLT images reflect TK1 activity and the percentage of cells in S phase.

Key Words: cell proliferation • fluorothymidine • 18F • thymidine kinase • tumors




This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
J. Leyton, G. Smith, M. Lees, M. Perumal, Q.-d. Nguyen, F. I. Aigbirhio, O. Golovko, Q. He, P. Workman, and E. O. Aboagye
Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901
Mol. Cancer Ther., September 1, 2008; 7(9): 3112 - 3121.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. Ullrich, H. Backes, H. Li, L. Kracht, H. Miletic, K. Kesper, B. Neumaier, W.-D. Heiss, K. Wienhard, and A. H. Jacobs
Glioma Proliferation as Assessed by 3'-Fluoro-3'-Deoxy-L-Thymidine Positron Emission Tomography in Patients with Newly Diagnosed High-Grade Glioma
Clin. Cancer Res., April 1, 2008; 14(7): 2049 - 2055.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. B. Solit, E. Santos, C. A. Pratilas, J. Lobo, M. Moroz, S. Cai, R. Blasberg, J. Sebolt-Leopold, S. Larson, and N. Rosen
3'-Deoxy-3'-[18F]Fluorothymidine Positron Emission Tomography Is a Sensitive Method for Imaging the Response of BRAF-Dependent Tumors to MEK Inhibition
Cancer Res., December 1, 2007; 67(23): 11463 - 11469.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
W. Chen, S. Delaloye, D. H.S. Silverman, C. Geist, J. Czernin, J. Sayre, N. Satyamurthy, W. Pope, A. Lai, M. E. Phelps, et al.
Predicting Treatment Response of Malignant Gliomas to Bevacizumab and Irinotecan by Imaging Proliferation With [18F] Fluorothymidine Positron Emission Tomography: A Pilot Study
J. Clin. Oncol., October 20, 2007; 25(30): 4714 - 4721.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
W. Chen
Clinical Applications of PET in Brain Tumors
J. Nucl. Med., September 1, 2007; 48(9): 1468 - 1481.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Herrmann, H. A. Wieder, A. K. Buck, M. Schoffel, B.-J. Krause, F. Fend, T. Schuster, C. Meyer zum Buschenfelde, H.-J. Wester, J. Duyster, et al.
Early Response Assessment Using 3'-Deoxy-3'-[18F]Fluorothymidine-Positron Emission Tomography in High-Grade Non-Hodgkin's Lymphoma
Clin. Cancer Res., June 15, 2007; 13(12): 3552 - 3558.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
A. R. Hsu, W. Cai, A. Veeravagu, K. A. Mohamedali, K. Chen, S. Kim, H. Vogel, L. C. Hou, V. Tse, M. G. Rosenblum, et al.
Multimodality Molecular Imaging of Glioblastoma Growth Inhibition with Vasculature-Targeting Fusion Toxin VEGF121/rGel
J. Nucl. Med., March 1, 2007; 48(3): 445 - 454.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
T. M. Blodgett, C. C. Meltzer, and D. W. Townsend
PET/CT: Form and Function
Radiology, February 1, 2007; 242(2): 360 - 385.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. K. Buck, M. Bommer, S. Stilgenbauer, M. Juweid, G. Glatting, H. Schirrmeister, T. Mattfeldt, D. Tepsic, D. Bunjes, F. M. Mottaghy, et al.
Molecular Imaging of Proliferation in Malignant Lymphoma.
Cancer Res., November 15, 2006; 66(22): 11055 - 11061.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
A. van Waarde, L. B. Been, K. Ishiwata, R. A. Dierckx, and P. H. Elsinga
Early Response of {sigma}-Receptor Ligands and Metabolic PET Tracers to 3 Forms of Chemotherapy: An In Vitro Study in Glioma Cells
J. Nucl. Med., September 1, 2006; 47(9): 1538 - 1545.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Leyton, J. P. Alao, M. Da Costa, A. V. Stavropoulou, J. R. Latigo, M. Perumal, R. Pillai, Q. He, P. Atadja, E. W.-F. Lam, et al.
In vivo Biological Activity of the Histone Deacetylase Inhibitor LAQ824 Is detectable with 3'-Deoxy-3'-[18F]Fluorothymidine Positron Emission Tomography.
Cancer Res., August 1, 2006; 66(15): 7621 - 7629.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Apisarnthanarax, M. M. Alauddin, F. Mourtada, H. Ariga, U. Raju, O. Mawlawi, D. Han, W. G. Bornmann, J. A. Ajani, L. Milas, et al.
Early Detection of Chemoradioresponse in Esophageal Carcinoma by 3'-Deoxy-3'-3H-Fluorothymidine Using Preclinical Tumor Models
Clin. Cancer Res., August 1, 2006; 12(15): 4590 - 4597.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
A. H. Jacobs, A. Thomas, L. W. Kracht, H. Li, C. Dittmar, G. Garlip, N. Galldiks, J. C. Klein, J. Sobesky, R. Hilker, et al.
18F-Fluoro-L-Thymidine and 11C-Methylmethionine as Markers of Increased Transport and Proliferation in Brain Tumors
J. Nucl. Med., December 1, 2005; 46(12): 1948 - 1958.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
J. R. Tseng, M. Dandekar, M. Subbarayan, Z. Cheng, J. M. Park, S. Louie, and S. S. Gambhir
Reproducibility of 3'-Deoxy-3'-18F-Fluorothymidine MicroPET Studies in Tumor Xenografts in Mice
J. Nucl. Med., November 1, 2005; 46(11): 1851 - 1857.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. M. Kenny, D. M. Vigushin, A. Al-Nahhas, S. Osman, S. K. Luthra, S. Shousha, R. C. Coombes, and E. O. Aboagye
Quantification of Cellular Proliferation in Tumor and Normal Tissues of Patients with Breast Cancer by [18F]Fluorothymidine-Positron Emission Tomography Imaging: Evaluation of Analytical Methods
Cancer Res., November 1, 2005; 65(21): 10104 - 10112.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
W. Chen, T. Cloughesy, N. Kamdar, N. Satyamurthy, M. Bergsneider, L. Liau, P. Mischel, J. Czernin, M. E. Phelps, and D. H.S. Silverman
Imaging Proliferation in Brain Tumors with 18F-FLT PET: Comparison with 18F-FDG
J. Nucl. Med., June 1, 2005; 46(6): 945 - 952.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Leyton, J. R. Latigo, M. Perumal, H. Dhaliwal, Q. He, and E. O. Aboagye
Early Detection of Tumor Response to Chemotherapy by 3'-Deoxy-3'-[18F]Fluorothymidine Positron Emission Tomography: The Effect of Cisplatin on a Fibrosarcoma Tumor Model In vivo
Cancer Res., May 15, 2005; 65(10): 4202 - 4210.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
M. Muzi, H. Vesselle, J. R. Grierson, D. A. Mankoff, R. A. Schmidt, L. Peterson, J. M. Wells, and K. A. Krohn
Kinetic Analysis of 3'-Deoxy-3'-Fluorothymidine PET Studies: Validation Studies in Patients with Lung Cancer
J. Nucl. Med., February 1, 2005; 46(2): 274 - 282.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
M. Muzi, D. A. Mankoff, J. R. Grierson, J. M. Wells, H. Vesselle, and K. A. Krohn
Kinetic Modeling of 3'-Deoxy-3'-Fluorothymidine in Somatic Tumors: Mathematical Studies
J. Nucl. Med., February 1, 2005; 46(2): 371 - 380.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
C. Waldherr, I. K. Mellinghoff, C. Tran, B. S. Halpern, N. Rozengurt, A. Safaei, W. A. Weber, D. Stout, N. Satyamurthy, J. Barrio, et al.
Monitoring Antiproliferative Responses to Kinase Inhibitor Therapy in Mice with 3'-Deoxy-3'-18F-Fluorothymidine PET
J. Nucl. Med., January 1, 2005; 46(1): 114 - 120.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
A. van Waarde, D. C.P. Cobben, A. J.H. Suurmeijer, B. Maas, W. Vaalburg, E. F.J. de Vries, P. L. Jager, H. J. Hoekstra, and P. H. Elsinga
Selectivity of 18F-FLT and 18F-FDG for Differentiating Tumor from Inflammation in a Rodent Model
J. Nucl. Med., April 1, 2004; 45(4): 695 - 700.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
G. Halter, A. K. Buck, H. Schirrmeister, I. Wurziger, F. Liewald, G. Glatting, B. Neumaier, L. Sunder-Plassmann, S. N. Reske, and M. Hetzel
[18F] 3-deoxy-3'-fluorothymidine positron emission tomography: Alternative or diagnostic adjunct to 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography in the workup of suspicious central focal lesions?
J. Thorac. Cardiovasc. Surg., April 1, 2004; 127(4): 1093 - 1099.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
N. Oyama, D. E. Ponde, C. Dence, J. Kim, Y.-C. Tai, and M. J. Welch
Monitoring of Therapy in Androgen-Dependent Prostate Tumor Model by Measuring Tumor Proliferation
J. Nucl. Med., March 1, 2004; 45(3): 519 - 525.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
H. Barthel, E. Aboagye, and P. Price
Reply
Cancer Res., December 1, 2003; 63(23): 8560 - 8560.
[Full Text] [PDF]

Home page
 JNMHome page
S. H. Britz-Cunningham and S. J. Adelstein
Molecular Targeting with Radionuclides: State of the Science
J. Nucl. Med., December 1, 2003; 44(12): 1945 - 1961.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
J. L. Schwartz, Y. Tamura, R. Jordan, J. R. Grierson, and K. A. Krohn
Monitoring Tumor Cell Proliferation by Targeting DNA Synthetic Processes with Thymidine and Thymidine Analogs
J. Nucl. Med., December 1, 2003; 44(12): 2027 - 2032.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Radiol.Home page
G J R Cook
Oncological molecular imaging: nuclear medicine techniques
Br. J. Radiol., December 1, 2003; 76(suppl_2): S152 - S158.
[Full Text] [PDF]

Home page
 GutHome page
D L Francis, A Freeman, D Visvikis, D C Costa, S K Luthra, M Novelli, I Taylor, and P J Ell
In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography
Gut, November 1, 2003; 52(11): 1602 - 1606.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
A. K. Buck, G. Halter, H. Schirrmeister, J. Kotzerke, I. Wurziger, G. Glatting, T. Mattfeldt, B. Neumaier, S. N. Reske, and M. Hetzel
Imaging Proliferation in Lung Tumors with PET: 18F-FLT Versus 18F-FDG
J. Nucl. Med., September 1, 2003; 44(9): 1426 - 1431.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
A. F. Shields
PET Imaging with 18F-FLT and Thymidine Analogs: Promise and Pitfalls
J. Nucl. Med., September 1, 2003; 44(9): 1432 - 1434.
[Full Text] [PDF]

Home page
 JNMHome page
H. Vesselle, J. Grierson, L. M. Peterson, M. Muzi, D. A. Mankoff, and K. A. Krohn
18F-Fluorothymidine Radiation Dosimetry in Human PET Imaging Studies
J. Nucl. Med., September 1, 2003; 44(9): 1482 - 1488.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Barthel, M. C. Cleij, D. R. Collingridge, O. C. Hutchinson, S. Osman, Q. He, S. K. Luthra, F. Brady, P. M. Price, and E. O. Aboagye
3'-Deoxy-3'-[18F]Fluorothymidine as a New Marker for Monitoring Tumor Response to Antiproliferative Therapy in Vivo with Positron Emission Tomography
Cancer Res., July 1, 2003; 63(13): 3791 - 3798.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Wagner, U. Seitz, A. Buck, B. Neumaier, S. Schultheiss, M. Bangerter, M. Bommer, F. Leithauser, E. Wawra, G. Munzert, et al.
3'-[18F]Fluoro-3'-Deoxythymidine ([18F]-FLT) as Positron Emission Tomography Tracer for Imaging Proliferation in a Murine B-Cell Lymphoma Model and in the Human Disease
Cancer Res., May 15, 2003; 63(10): 2681 - 2687.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY THE JOURNAL OF NUCLEAR MEDICINE
Copyright © 2002 by the Society of Nuclear Medicine.