Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2011

01-01-2011 | Original Article

Early response assessment in prostate carcinoma by 18F-fluorothymidine following anticancer therapy with docetaxel using preclinical tumour models

Authors: Nobuyuki Oyama, Yoko Hasegawa, Yasushi Kiyono, Masato Kobayashi, Yasuhisa Fujibayashi, Datta E. Ponde, Carmen Dence, Michael J. Welch, Osamu Yokoyama

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2011

Login to get access

Abstract

Purpose

The aim of the study was to assess the potential usefulness of 3-deoxy-3-18F-fluorothymidine (FLT) as a radiopharmaceutical for imaging the early therapeutic effects of docetaxel (DTX) on tumour proliferation in hormone-refractory prostate cancer (HRPC).

Methods

Cells of the androgen-independent human prostate tumour cell line, 22Rv1, were implanted in athymic male mice. Approximately 3 weeks after cell implantation, the mice were treated with DTX or vehicle. Before and after the treatment, the mice were imaged with a microPET-Focus-F120 scanner (Concorde Microsystems, Knoxville, TN, USA) using FLT and 18F-fluorodeoxyglucose (FDG). Tracer accumulations in the tumours were then analysed and compared with the proliferation activity and apoptotic index of the tumours. In a separate cell study, 22Rv1 cells were treated with DTX, then incubated with FLT or FDG and examined for their tracer uptake.

Results

The microPET imaging showed a significant decrease of FLT uptake in tumours after administration of DTX, while the changes of FDG uptake were minimal. Immunohistochemical analysis of the tumours revealed that the changes of FLT uptake were well correlated with those of proliferation activity but not with the apoptotic index. In vitro studies demonstrated that the significant decrease of FLT uptake in the cells after incubation with DTX correlated with the % S-phase cell fraction, while there were only minimal changes in the prostate-specific antigen concentration of the cell medium and FDG uptake in the cells.

Conclusion

These results indicate that FLT is a promising tracer for monitoring the early effects of anticancer therapy with DTX in patients with HRPC.
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225–49.CrossRefPubMed Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225–49.CrossRefPubMed
2.
go back to reference Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293–7. Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293–7.
3.
go back to reference Eisenberger MA. Chemotherapy for prostate carcinoma. NCI Monogr 1988;7:151–63.PubMed Eisenberger MA. Chemotherapy for prostate carcinoma. NCI Monogr 1988;7:151–63.PubMed
4.
go back to reference Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513–20.CrossRefPubMed Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513–20.CrossRefPubMed
5.
go back to reference Oyama N, Kim J, Jones LA, Mercer NM, Engelbach JA, Sharp TL, et al. MicroPET assessment of androgenic control of glucose and acetate uptake in the rat prostate and a prostate cancer tumor model. Nucl Med Biol 2002;29:783–90.CrossRefPubMed Oyama N, Kim J, Jones LA, Mercer NM, Engelbach JA, Sharp TL, et al. MicroPET assessment of androgenic control of glucose and acetate uptake in the rat prostate and a prostate cancer tumor model. Nucl Med Biol 2002;29:783–90.CrossRefPubMed
6.
go back to reference Oyama N, Akino H, Suzuki Y, Kanamaru H, Ishida H, Tanase K, et al. FDG PET for evaluating the change of glucose metabolism in prostate cancer after androgen ablation. Nucl Med Commun 2001;22:963–9.CrossRefPubMed Oyama N, Akino H, Suzuki Y, Kanamaru H, Ishida H, Tanase K, et al. FDG PET for evaluating the change of glucose metabolism in prostate cancer after androgen ablation. Nucl Med Commun 2001;22:963–9.CrossRefPubMed
7.
go back to reference Kurdziel KA, Figg WD, Carrasquillo JA, Huebsch S, Whatley M, Sellers D, et al. Using positron emission tomography 2-deoxy-2-[18F]fluoro-D-glucose, 11CO, and 15O-water for monitoring androgen independent prostate cancer. Mol Imaging Biol 2003;5:86–93.CrossRefPubMed Kurdziel KA, Figg WD, Carrasquillo JA, Huebsch S, Whatley M, Sellers D, et al. Using positron emission tomography 2-deoxy-2-[18F]fluoro-D-glucose, 11CO, and 15O-water for monitoring androgen independent prostate cancer. Mol Imaging Biol 2003;5:86–93.CrossRefPubMed
8.
go back to reference Effert PJ, Bares R, Handt S, Wolff JM, Büll D, Jakse G. Metabolic imaging of untreated prostate cancer by positron emission tomography with 18fluorine-labeled deoxyglucose. J Urol 1996;155:994–8.CrossRefPubMed Effert PJ, Bares R, Handt S, Wolff JM, Büll D, Jakse G. Metabolic imaging of untreated prostate cancer by positron emission tomography with 18fluorine-labeled deoxyglucose. J Urol 1996;155:994–8.CrossRefPubMed
9.
go back to reference Oyama N, Akino H, Suzuki Y, Kanamaru H, Sadato N, Yonekura Y, et al. The increased accumulation of [18F]fluorodeoxyglucose in untreated prostate cancer. Jpn J Clin Oncol 1999;29:623–9.CrossRefPubMed Oyama N, Akino H, Suzuki Y, Kanamaru H, Sadato N, Yonekura Y, et al. The increased accumulation of [18F]fluorodeoxyglucose in untreated prostate cancer. Jpn J Clin Oncol 1999;29:623–9.CrossRefPubMed
10.
go back to reference Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 1998;39:990–5.PubMed Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 1998;39:990–5.PubMed
11.
go back to reference DeGrado TR, Baldwin SW, Wang S, Orr MD, Liao RP, Friedman HS, et al. Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers. J Nucl Med 2001;42:1805–14.PubMed DeGrado TR, Baldwin SW, Wang S, Orr MD, Liao RP, Friedman HS, et al. Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers. J Nucl Med 2001;42:1805–14.PubMed
12.
go back to reference Oyama N, Akino H, Kanamaru H, Suzuki Y, Muramoto S, Yonekura Y, et al. 11C-acetate PET imaging of prostate cancer. J Nucl Med 2002;43:181–6.PubMed Oyama N, Akino H, Kanamaru H, Suzuki Y, Muramoto S, Yonekura Y, et al. 11C-acetate PET imaging of prostate cancer. J Nucl Med 2002;43:181–6.PubMed
13.
go back to reference Yoshimoto M, Waki A, Yonekura Y, Sadato N, Murata T, Omata N, et al. Characterization of acetate metabolism in tumor cells in relation to cell proliferation: acetate metabolism in tumor cells. Nucl Med Biol 2001;28:117–22.CrossRefPubMed Yoshimoto M, Waki A, Yonekura Y, Sadato N, Murata T, Omata N, et al. Characterization of acetate metabolism in tumor cells in relation to cell proliferation: acetate metabolism in tumor cells. Nucl Med Biol 2001;28:117–22.CrossRefPubMed
14.
go back to reference Yoshimoto M, Waki A, Obata A, Furukawa T, Yonekura Y, Fujibayashi Y. Radiolabeled choline as a proliferation marker: comparison with radiolabeled acetate. Nucl Med Biol 2004;31:859–65.CrossRefPubMed Yoshimoto M, Waki A, Obata A, Furukawa T, Yonekura Y, Fujibayashi Y. Radiolabeled choline as a proliferation marker: comparison with radiolabeled acetate. Nucl Med Biol 2004;31:859–65.CrossRefPubMed
15.
go back to reference Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 1998;4:1334–6.CrossRefPubMed Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 1998;4:1334–6.CrossRefPubMed
16.
go back to reference Buck AK, Schirrmeister H, Hetzel M, Von Der Heide M, Halter G, Glatting G, et al. 3-Deoxy-3-[18F]fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res 2002;62:3331–4.PubMed Buck AK, Schirrmeister H, Hetzel M, Von Der Heide M, Halter G, Glatting G, et al. 3-Deoxy-3-[18F]fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res 2002;62:3331–4.PubMed
17.
go back to reference Vesselle H, Grierson J, Muzi M, Pugsley JM, Schmidt RA, Rabinowitz P, et al. In vivo validation of 3'deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin Cancer Res 2002;8:3315–23.PubMed Vesselle H, Grierson J, Muzi M, Pugsley JM, Schmidt RA, Rabinowitz P, et al. In vivo validation of 3'deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin Cancer Res 2002;8:3315–23.PubMed
18.
go back to reference Pio BS, Park CK, Pietras R, Hsueh WA, Satyamurthy N, Pegram MD, et al. Usefulness of 3'-[F-18]fluoro-3'-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol Imaging Biol 2006;8:36–42.CrossRefPubMed Pio BS, Park CK, Pietras R, Hsueh WA, Satyamurthy N, Pegram MD, et al. Usefulness of 3'-[F-18]fluoro-3'-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol Imaging Biol 2006;8:36–42.CrossRefPubMed
19.
go back to reference Ponde DE, Oyama N, Welch MJ, McCarthy TJ. Synthesis of fluorothymidine ([18F]FLT) for radiotracer of tumors. Abstr Pap AM Chem S 2002;223:081-Nucl Part 2. Ponde DE, Oyama N, Welch MJ, McCarthy TJ. Synthesis of fluorothymidine ([18F]FLT) for radiotracer of tumors. Abstr Pap AM Chem S 2002;223:081-Nucl Part 2.
20.
go back to reference Tai YC, Chatziioannou A, Siegel S, Young J, Newport D, Goble RN, et al. Performance evaluation of the microPET P4: a PET system dedicated to animal imaging. Phys Med Biol 2001;46:1845–62.CrossRefPubMed Tai YC, Chatziioannou A, Siegel S, Young J, Newport D, Goble RN, et al. Performance evaluation of the microPET P4: a PET system dedicated to animal imaging. Phys Med Biol 2001;46:1845–62.CrossRefPubMed
21.
go back to reference Shields AF, Lim K, Grierson J, Link J, Krohn KA. Utilization of labeled thymidine in DNA synthesis: studies for PET. J Nucl Med 1990;31:337–42.PubMed Shields AF, Lim K, Grierson J, Link J, Krohn KA. Utilization of labeled thymidine in DNA synthesis: studies for PET. J Nucl Med 1990;31:337–42.PubMed
22.
go back to reference Goethals P, van Eijkeren M, Lodewyck W, Dams R. Measurement of [methyl-carbon-11]thymidine and its metabolites in head and neck tumors. J Nucl Med 1995;36:880–2.PubMed Goethals P, van Eijkeren M, Lodewyck W, Dams R. Measurement of [methyl-carbon-11]thymidine and its metabolites in head and neck tumors. J Nucl Med 1995;36:880–2.PubMed
23.
go back to reference Shields AF, Mankoff DA, Link JM, Graham MM, Eary JF, Kozawa SM, et al. Carbon-11-thymidine and FDG to measure therapy response. J Nucl Med 1998;39:1757–62.PubMed Shields AF, Mankoff DA, Link JM, Graham MM, Eary JF, Kozawa SM, et al. Carbon-11-thymidine and FDG to measure therapy response. J Nucl Med 1998;39:1757–62.PubMed
24.
go back to reference Wells JM, Mankoff DA, Muzi M, O’Sullivan F, Eary JF, Spence AM, et al. Kinetic analysis of 2-[11C]thymidine PET imaging studies of malignant brain tumors: compartmental model investigation and mathematical analysis. Mol Imaging 2002;1:151–9.CrossRefPubMed Wells JM, Mankoff DA, Muzi M, O’Sullivan F, Eary JF, Spence AM, et al. Kinetic analysis of 2-[11C]thymidine PET imaging studies of malignant brain tumors: compartmental model investigation and mathematical analysis. Mol Imaging 2002;1:151–9.CrossRefPubMed
25.
go back to reference Rasey JS, Grierson JR, Wiens LW, Kolb PD, Schwartz JL. Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med 2002;43:1210–7.PubMed Rasey JS, Grierson JR, Wiens LW, Kolb PD, Schwartz JL. Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med 2002;43:1210–7.PubMed
26.
go back to reference Dittmann H, Dohmen BM, Kehlbach R, Bartusek G, Pritzkow M, Sarbia M, et al. Early changes in [18F]FLT uptake after chemotherapy: an experimental study. Eur J Nucl Med Mol Imaging 2002;29:1462–9.CrossRefPubMed Dittmann H, Dohmen BM, Kehlbach R, Bartusek G, Pritzkow M, Sarbia M, et al. Early changes in [18F]FLT uptake after chemotherapy: an experimental study. Eur J Nucl Med Mol Imaging 2002;29:1462–9.CrossRefPubMed
27.
go back to reference Ebenhan T, Honer M, Ametamey SM, Schubiger PA, Becquet M, Ferretti S, et al. Comparison of [18F]-tracers in various experimental tumor models by PET imaging and identification of an early response biomarker for the novel microtubule stabilizer patupilone. Mol Imaging Biol 2009;11:308–21.CrossRefPubMed Ebenhan T, Honer M, Ametamey SM, Schubiger PA, Becquet M, Ferretti S, et al. Comparison of [18F]-tracers in various experimental tumor models by PET imaging and identification of an early response biomarker for the novel microtubule stabilizer patupilone. Mol Imaging Biol 2009;11:308–21.CrossRefPubMed
28.
go back to reference Altmann KH. Epothilone B and its analogs – a new family of anticancer agents. Mini Rev Med Chem 2003;3:149–58.CrossRefPubMed Altmann KH. Epothilone B and its analogs – a new family of anticancer agents. Mini Rev Med Chem 2003;3:149–58.CrossRefPubMed
29.
go back to reference Yue J, Chen L, Cabrera AR, Sun X, Zhao S, Zheng F, et al. Measuring tumor cell proliferation with 18F-FLT PET during radiotherapy of esophageal squamous cell carcinoma: a pilot clinical study. J Nucl Med 2010;51:528–34.CrossRefPubMed Yue J, Chen L, Cabrera AR, Sun X, Zhao S, Zheng F, et al. Measuring tumor cell proliferation with 18F-FLT PET during radiotherapy of esophageal squamous cell carcinoma: a pilot clinical study. J Nucl Med 2010;51:528–34.CrossRefPubMed
Metadata
Title
Early response assessment in prostate carcinoma by 18F-fluorothymidine following anticancer therapy with docetaxel using preclinical tumour models
Authors
Nobuyuki Oyama
Yoko Hasegawa
Yasushi Kiyono
Masato Kobayashi
Yasuhisa Fujibayashi
Datta E. Ponde
Carmen Dence
Michael J. Welch
Osamu Yokoyama
Publication date
01-01-2011
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2011
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-010-1613-z

Other articles of this Issue 1/2011

European Journal of Nuclear Medicine and Molecular Imaging 1/2011 Go to the issue

Society communications

Oops ... we did it again!

Image of the Month

Don’t blame the bones!