| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Investigations |
Division of Nuclear Medicine [J. F. E., D. A. M., A. O., J. M. L., F. O’S., K. A. K.], and Departments of Neurology [A. M. S.] and Neurosurgery [M. S. B.], University of Washington Medical Center, Seattle, Washington 98195-6113
Malignant brain tumors pose diagnostic and therapeutic problems. Despite the advent of new brain imaging modalities, including magnetic resonance imaging (MRI) and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), determination of tumor viability and response to treatment is often difficult. Blood-brain barrier disruption can be caused by tumor or nonspecific reactions to treatment, making MRI interpretation ambiguous. The high metabolic background of the normal brain and its regional variability makes it difficult to identify small or less active tumors by FDG imaging of cellular energetics. We have investigated 2-[C-11]thymidine (dThd) and PET to image the rate of brain tumor cellular proliferation. A series of 13 patients underwent closely spaced dThd PET, FDG PET, and MRI procudures, and the image results were compared by standardized visual analysis. The resulting dThd scans were qualitatively different from the other two scans in approximately 50% of the cases, which suggests that dThd provided information distinct from FDG PET and MRI. In two cases, recurrent tumor was more apparent on the dThd study than on FDG; in two other patients, tumor dThd uptake was less than FDG uptake, and these patients had slower tumor progression than the three patients with both high dThd and FDG uptake. To better characterize tumor proliferation, kinetic modeling was applied to dynamic dThd PET uptake data and metabolite-analyzed blood data in a subset of patients. Kinetic analysis was able to remove the confounding influence of [C-11]CO2, the principal labeled metabolite of 2-[C-11]dThd, and to estimate the flux of dThd incorporation into DNA. Sequential, same-day [C-11]CO2 and [C-11]dThd imaging demonstrated the ability of kinetic analysis to model both dThd and CO2 simultaneously. Images of dThd flux obtained using the model along with the mixture analysis method for pixel-by-pixel parametric imaging significantly enhanced the contrast of tumor compared with normal brain. Comparison of model estimates of dThd transport versus dThd flux was able to discern increased dThd uptake simply on the basis of blood-brain barrier disruption from retention on the basis of increased cellular proliferation. This preliminary study demonstrates the potential for imaging brain tumor cellular proliferation to provide unique information for guiding patient treatment.
This article has been cited by other articles:
|
|
 |
|
  J. R. Bading and A. F. Shields Imaging of Cell Proliferation: Status and Prospects J. Nucl. Med., June 1, 2008; 49(Suppl_2): 64S - 80S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Muzi, A. M. Spence, F. O'Sullivan, D. A. Mankoff, J. M. Wells, J. R. Grierson, J. M. Link, and K. A. Krohn Kinetic Analysis of 3'-Deoxy-3'-18F-Fluorothymidine in Patients with Gliomas J. Nucl. Med., October 1, 2006; 47(10): 1612 - 1621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Workman, E. O. Aboagye, Y.-L. Chung, J. R. Griffiths, R. Hart, M. O. Leach, R. J. Maxwell, P. M. J. McSheehy, P. M. Price, and J. Zweit Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies. J Natl Cancer Inst, May 3, 2006; 98(9): 580 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
H. Sun, T. J. Mangner, J. M. Collins, O. Muzik, K. Douglas, and A. F. Shields Imaging DNA Synthesis In Vivo with 18F-FMAU and PET J. Nucl. Med., February 1, 2005; 46(2): 292 - 296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 B M Seddon and P Workman The role of functional and molecular imaging in cancer drug discovery and development Br. J. Radiol., December 1, 2003; 76(suppl_2): S128 - S138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
J. Toyohara, A. Gogami, A. Hayashi, Y. Yonekura, and Y. Fujibayashi Pharmacokinetics and Metabolism of 5-125I-Iodo-4'-Thio-2'-Deoxyuridine in Rodents J. Nucl. Med., October 1, 2003; 44(10): 1671 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 H. Vesselle, J. Grierson, M. Muzi, J. M. Pugsley, R. A. Schmidt, P. Rabinowitz, L. M. Peterson, E. Vallieres, and D. E. Wood In Vivo Validation of 3'deoxy-3'-[18F]fluorothymidine ([18F]FLT) as a Proliferation Imaging Tracer in Humans: Correlation of [18F]FLT Uptake by Positron Emission Tomography with Ki-67 Immunohistochemistry and Flow Cytometry in Human Lung Tumors Clin. Cancer Res., November 1, 2002; 8(11): 3315 - 3323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wells, R. N. Gunn, M. Alison, C. Steel, M. Golding, A. S. Ranicar, F. Brady, S. Osman, T. Jones, and P. Price Assessment of Proliferation in Vivo Using 2-[11C]Thymidine Positron Emission Tomography in Advanced Intra-abdominal Malignancies Cancer Res., October 15, 2002; 62(20): 5698 - 5702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Rasey, J. R. Grierson, L. W. Wiens, P. D. Kolb, and J. L. Schwartz Validation of FLT Uptake as a Measure of Thymidine Kinase-1 Activity in A549 Carcinoma Cells J. Nucl. Med., September 1, 2002; 43(9): 1210 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Dupertuis, M. Vazquez, J.-P. Mach, N. De Tribolet, C. Pichard, D. O. Slosman, and F. Buchegger Fluorodeoxyuridine Improves Imaging of Human Glioblastoma Xenografts with Radiolabeled Iododeoxyuridine Cancer Res., November 1, 2001; 61(21): 7971 - 7977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Seitz, M. Wagner, A. T. Vogg, G. Glatting, B. Neumaier, F. R. Greten, R. M. Schmid, and S. N. Reske In Vivo Evaluation of 5-[18F]Fluoro-2'-deoxyuridine as Tracer for Positron Emission Tomography in a Murine Pancreatic Cancer Model Cancer Res., May 1, 2001; 61(10): 3853 - 3857. [Abstract] [Full Text]
|
|
|
|
|
|
R. G. Blasberg, U. Roelcke, R. Weinreich, B. Beattie, K. von Ammon, Y. Yonekawa, H. Landolt, I. Guenther, N. E. A. Crompton, P. Vontobel, et al. Imaging Brain Tumor Proliferative Activity with [124I]Iododeoxyuridine Cancer Res., February 1, 2000; 60(3): 624 - 635. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
