HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Waldherr, C. Articles by Czernin, J. Search for Related Content PubMed PubMed Citation Articles by Waldherr, C. Articles by Czernin, J.

Monitoring Antiproliferative Responses to Kinase Inhibitor Therapy in Mice with 3'-Deoxy-3'-¹⁸F-Fluorothymidine PET

¹ Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
² Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
³ Howard Hughes Medical Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
⁴ Department of Pathology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
⁵ Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
⁶ Molecular Biology Institute, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California

The aim of this study was to evaluate, whether PET with ¹⁸F-FDG and 3'-deoxy-3'-¹⁸F-fluorothymidine (¹⁸F-FLT) may be used to monitor noninvasively the antiproliferative effects of tyrosine kinase inhibitors. Methods: Using a high-resolution small animal scanner, we measured the effect of the ErbB-selective kinase inhibitor PKI-166 on the ¹⁸F-FDG and ¹⁸F-FLT uptake of ErbB1-overexpressing A431 xenograft tumors. Results: Treatment with PKI-166 markedly lowered tumor ¹⁸F-FLT uptake within 48 h of drug exposure; within 1 wk ¹⁸F-FLT uptake decreased by 79%. ¹⁸F-FLT uptake by the xenografts significantly correlated with the tumor proliferation index as determined by proliferating cell nuclear antigen staining (r = 0.71). Changes in ¹⁸F-FLT uptake did not reflect inhibition of ErbB kinase activity itself but, rathe, the effects of kinase inhibition on tumor cell proliferation. Tumor ¹⁸F-FDG uptake generally paralleled the changes seen for ¹⁸F-FLT. However, the baseline signal was significantly lower than that for ¹⁸F-FLT. Conclusion: These results indicate that ¹⁸F-FLT PET provides noninvasive, quantitative, and repeatable measurements of tumor cell proliferation during treatment with ErbB kinase inhibitors and provide a rationale for the use this technology in clinical trials of kinase inhibitors.

Key Words: thymidine kinase • ErbB • small molecule kinase inhibitor • ¹⁸F-FDG PET • ¹⁸F-FLT PET

Related articles in JNM:

THIS MONTH IN JNM

JNM 2005 46: 8a-9a. [Full Text]  

This article has been cited by other articles:

				M. P.S. Dunphy and J. S. Lewis Radiopharmaceuticals in Preclinical and Clinical Development for Monitoring of Therapy with PET J. Nucl. Med., May 1, 2009; 50(Suppl_1): 106S - 121S. [Abstract] [Full Text] [PDF]

				S. J. Kim, J. S. Lee, K. C. Im, S.-Y. Kim, S.-A. Park, S. J. Lee, S. J. Oh, D. S. Lee, and D. H. Moon Kinetic Modeling of 3'-Deoxy-3'-18F-Fluorothymidine for Quantitative Cell Proliferation Imaging in Subcutaneous Tumor Models in Mice J. Nucl. Med., December 1, 2008; 49(12): 2057 - 2066. [Abstract] [Full Text] [PDF]

				R. H. Brown, C. G. Irvin, G. B. Allen III, S. D. Shapiro, W. J. Martin, M. R. J. Kolb, D. M. Hyde, G. F. Nieman, D. D. Cody, M. Ishii, et al. An Official ATS Conference Proceedings: Advances in Small-Animal Imaging Application to Lung Pathophysiology Proceedings of the ATS, July 15, 2008; 5(5): 591 - 600. [Full Text] [PDF]

				L. H. Wei, H. Su, I. J. Hildebrandt, M. E. Phelps, J. Czernin, and W. A. Weber Changes in Tumor Metabolism as Readout for Mammalian Target of Rapamycin Kinase Inhibition by Rapamycin in Glioblastoma Clin. Cancer Res., June 1, 2008; 14(11): 3416 - 3426. [Abstract] [Full Text] [PDF]

				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. S. Bradbury, D. Hambardzumyan, P. B. Zanzonico, J. Schwartz, S. Cai, E. M. Burnazi, V. Longo, S. M. Larson, and E. C. Holland Dynamic Small-Animal PET Imaging of Tumor Proliferation with 3'-Deoxy-3'-18F-Fluorothymidine in a Genetically Engineered Mouse Model of High-Grade Gliomas J. Nucl. Med., March 1, 2008; 49(3): 422 - 429. [Abstract] [Full Text] [PDF]

				J. R. Tseng, K. W. Kang, M. Dandekar, S. Yaghoubi, J. H. Lee, J. G. Christensen, S. Muir, P. W. Vincent, N. R. Michaud, and S. S. Gambhir Preclinical Efficacy of the c-Met Inhibitor CE-355621 in a U87 MG Mouse Xenograft Model Evaluated by 18F-FDG Small-Animal PET J. Nucl. Med., January 1, 2008; 49(1): 129 - 134. [Abstract] [Full Text] [PDF]

				H. Su, C. Bodenstein, R. A. Dumont, Y. Seimbille, S. Dubinett, M. E. Phelps, H. Herschman, J. Czernin, and W. Weber Monitoring Tumor Glucose Utilization by Positron Emission Tomography for the Prediction of Treatment Response to Epidermal Growth Factor Receptor Kinase Inhibitors. Clin. Cancer Res., October 1, 2006; 12(19): 5659 - 5667. [Abstract] [Full Text] [PDF]

				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]

				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]

				W. A. Weber Positron Emission Tomography As an Imaging Biomarker J. Clin. Oncol., July 10, 2006; 24(20): 3282 - 3292. [Abstract] [Full Text] [PDF]

				B. J. Fueger, J. Czernin, I. Hildebrandt, C. Tran, B. S. Halpern, D. Stout, M. E. Phelps, and W. A. Weber Impact of Animal Handling on the Results of 18F-FDG PET Studies in Mice J. Nucl. Med., June 1, 2006; 47(6): 999 - 1006. [Abstract] [Full Text] [PDF]

				W. A. Weber Chaperoning Drug Development with PET J. Nucl. Med., May 1, 2006; 47(5): 735 - 737. [Full Text] [PDF]

				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]