This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Wagner, M. Articles by Reske, S. N. Search for Related Content PubMed PubMed Citation Articles by Wagner, M. Articles by Reske, S. N.

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

Departments of Nuclear Medicine [U. S., A. B., B. N., S. S., S. N. R], Internal Medicine I [M. W., M. Ba.], Internal Medicine III [M. Bo., G. M.], Pathology [F. L.], University of Ulm, 89081 Ulm, Germany and Vienna Biocenter, Institute of Molecular Biology, University of Vienna, A-1030 Vienna [E. W.]

Here we describe the evaluation of 3'-[¹⁸F]fluoro-3'-deoxythymidine {[¹⁸F]-FLT} as a tracer for positron emission tomography (PET) in a murine model of B-cell lymphoma and in human malignant lymphoma. The human B-cell line DoHH2 expressed high levels of active thymidine kinase 1 (TK-1) as the key enzyme of [¹⁸F]-FLT metabolism. Immunostaining confirmed high levels of TK-1 in DoHH2 derived xenograft tumors in SCID/SCID mice. In vitro studies demonstrated a time-dependent uptake of [¹⁸F]-FLT, an efficient phosphorylation to the respective monophosphate and the incorporation of [¹⁸F]-FLT into the perchloric acid insoluble fraction in DoHH2 cells, indicating the incorporation of this tracer into the DNA. After incubation with [¹⁸F]FLT for 240 min, 12.5% ± 1.0% of radioactivity applied to the medium was intracellularly trapped in DoHH2 cells. Specific accumulation of [¹⁸F]-FLT in the malignant cell clone was confirmed in biodistribution studies in SCID/SCID mice bearing DoHH2-derived tumors. The percentage of injected dose of [¹⁸F]-FLT per gram of tumor tissue correlated with the tumor-proliferation index as evaluated in BrdUrd-labeling experiments. In a pilot study of 11 patients with both indolent and aggressive lymphoma, [¹⁸F]-FLT was suitable and comparable to [¹⁸F]-FDG in the ability to detect malignant lesions by PET scan. Furthermore, we found a close correlation (r = 0.95, P < 0.005) of the [¹⁸F]-FLT standardized uptake values with the Ki67-labeling index of tissue biopsies (n = 10) in these patients. These results suggest that [¹⁸F]-FLT represents a novel tracer for PET that enables imaging of proliferation in human lymphoma in vivo.

This article has been cited by other articles:

				C. Murayama, N. Harada, T. Kakiuchi, D. Fukumoto, A. Kamijo, A. T. Kawaguchi, and H. Tsukada Evaluation of D-18F-FMT, 18F-FDG, L-11C-MET, and 18F-FLT for Monitoring the Response of Tumors to Radiotherapy in Mice J. Nucl. Med., February 1, 2009; 50(2): 290 - 295. [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]

				A. K. Buck, M. Bommer, M. E. Juweid, G. Glatting, S. Stilgenbauer, F. M. Mottaghy, M. Schulz, T. Kull, D. Bunjes, P. Moller, et al. First Demonstration of Leukemia Imaging with the Proliferation Marker 18F-Fluorodeoxythymidine J. Nucl. Med., November 1, 2008; 49(11): 1756 - 1762. [Abstract] [Full Text] [PDF]

				K. Herrmann, F. Eckel, S. Schmidt, K. Scheidhauer, B. J. Krause, J. Kleeff, T. Schuster, H.-J. Wester, H. Friess, R. M. Schmid, et al. In Vivo Characterization of Proliferation for Discriminating Cancer from Pancreatic Pseudotumors J. Nucl. Med., September 1, 2008; 49(9): 1437 - 1444. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

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

				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]

				C. C. Riedl, T. Akhurst, S. Larson, S. F. Stanziale, S. Tuorto, A. Bhargava, H. Hricak, D. Klimstra, and Y. Fong 18F-FDG PET Scanning Correlates with Tissue Markers of Poor Prognosis and Predicts Mortality for Patients After Liver Resection for Colorectal Metastases J. Nucl. Med., May 1, 2007; 48(5): 771 - 775. [Abstract] [Full Text] [PDF]

				L. B. Been, A. J.H. Suurmeijer, P. H. Elsinga, P. L. Jager, R. J. van Ginkel, and H. J. Hoekstra 18F-Fluorodeoxythymidine PET for Evaluating the Response to Hyperthermic Isolated Limb Perfusion for Locally Advanced Soft-Tissue Sarcomas J. Nucl. Med., March 1, 2007; 48(3): 367 - 372. [Abstract] [Full Text] [PDF]

				A. H. Jacobs, M. A. Rueger, A. Winkeler, H. Li, S. Vollmar, Y. Waerzeggers, B. Rueckriem, C. Kummer, C. Dittmar, M. Klein, et al. Imaging-Guided Gene Therapy of Experimental Gliomas Cancer Res., February 15, 2007; 67(4): 1706 - 1715. [Abstract] [Full Text] [PDF]

				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]

				Y. S. Jhanwar and D. J. Straus The Role of PET in Lymphoma J. Nucl. Med., August 1, 2006; 47(8): 1326 - 1334. [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]

				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]

				A-L Grosu, M Piert, and M Molls Experience of PET for target localisation in radiation oncology Br. J. Radiol., November 1, 2005; Supplement_28(1): 18 - 32. [Full Text] [PDF]

				M. E. Juweid and B. D. Cheson Role of Positron Emission Tomography in Lymphoma J. Clin. Oncol., July 20, 2005; 23(21): 4577 - 4580. [Full Text] [PDF]

				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]

				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]

				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]

				M. Sugiyama, H. Sakahara, K. Sato, N. Harada, D. Fukumoto, T. Kakiuchi, T. Hirano, E. Kohno, and H. Tsukada Evaluation of 3'-Deoxy-3'-18F-Fluorothymidine for Monitoring Tumor Response to Radiotherapy and Photodynamic Therapy in Mice J. Nucl. Med., October 1, 2004; 45(10): 1754 - 1758. [Abstract] [Full Text] [PDF]

				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]

				J. D. Bradley, C. A. Perez, F. Dehdashti, and B. A. Siegel Implementing Biologic Target Volumes in Radiation Treatment Planning for Non-Small Cell Lung Cancer J. Nucl. Med., January 1, 2004; 45(90010): 96S - 101. [Abstract] [Full Text] [PDF]

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

				D. C.P. Cobben, P. H. Elsinga, A. van Waarde, and P. L. Jager Correspondence re: H. Barthel et al., 3'-Deoxy-3'-[18F]fluorothymidine as a New Marker for Monitoring Tumor Response to Antiproliferative Therapy in Vivo with Positron Emission Tomography. Cancer Res., 63: 3791-3798, 2003. Cancer Res., December 1, 2003; 63(23): 8558 - 8559. [Full Text] [PDF]

				J. W. Friedberg and V. Chengazi PET Scans in the Staging of Lymphoma: Current Status Oncologist, October 1, 2003; 8(5): 438 - 447. [Abstract] [Full Text] [PDF]