Skip to main content
Top
Published in: European Journal of Nuclear Medicine and Molecular Imaging 3/2009

01-03-2009 | Original Article

Early evaluation of the effects of chemotherapy with longitudinal FDG small-animal PET in human testicular cancer xenografts: early flare response does not reflect refractory disease

Authors: Nicolas Aide, Laurent Poulain, Mélanie Briand, Soizic Dutoit, Stéphane Allouche, Alexandre Labiche, Aurélie Ngo-Van Do, Valérie Nataf, Alain Batalla, Pascal Gauduchon, Jean-noël Talbot, Françoise Montravers

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2009

Login to get access

Abstract

Aim

We aimed to evaluate the usefulness of FDG PET in the early prediction of the effects of chemotherapy on human testicular cancer xenografts.

Material and methods

Nude rats bearing subcutaneous human embryonal carcinoma xenografts received either cisplatin (5 mg/kg) or saline serum. Small-animal PET studies were performed on days 0, 2, 4 and 7 and compared to immunochemistry studies, flow cytometry studies and hexokinase assays.

Results

Cisplatin treatment resulted in biphasic FDG uptake evolution: a peak was observed on day 2, followed by a marked decrease on day 7 despite an insignificant change in tumour volume. Similarly, a peak in cyclin A immunostaining was observed on days 2 and 4), followed by a significant decrease on day 7. Flow cytometry showed that the cyclin A peak was not related to increased cell proliferation but was due to a transient S and G2/M cell cycle arrest. A marked increase in cell apoptosis was observed from day 2 to day 7. GLUT-1 showed a significant decrease on day 7. Macrophagic infiltrate remained stable except for an increase observed on day 7. In control tumours, continuous growth was observed, all immunostaining markers remaining stable over time. Hexokinase activity was significantly lower on day 7 in treated tumours than in controls.

Conclusion

FDG PET may be useful in the early evaluation of treatment in patients with testicular cancer. In our model, a very early increased [18F]-FDG uptake was related to a transient cell cycle arrest and early stage apoptosis but did not reveal refractory disease.
Literature
1.
go back to reference Bourguet P, Blanc-Vincent MP, Boneu A, Bosquet L, Chauffert B, Corone C, et al. Summary of the Standards, Options and Recommendations for the use of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDP-PET scanning) in oncology (2002). Br J Cancer 2003;89(Suppl 1):S84–91.PubMedCrossRef Bourguet P, Blanc-Vincent MP, Boneu A, Bosquet L, Chauffert B, Corone C, et al. Summary of the Standards, Options and Recommendations for the use of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDP-PET scanning) in oncology (2002). Br J Cancer 2003;89(Suppl 1):S84–91.PubMedCrossRef
2.
go back to reference Avril N, Sassen S, Schmalfeldt B, Naehrig J, Rutke S, Weber WA, et al. Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer. J Clin Oncol 2005;23:7445–53.PubMedCrossRef Avril N, Sassen S, Schmalfeldt B, Naehrig J, Rutke S, Weber WA, et al. Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer. J Clin Oncol 2005;23:7445–53.PubMedCrossRef
3.
go back to reference Rousseau C, Devillers A, Sagan C, Ferrer L, Bridji B, Campion L, et al. Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F]fluorodeoxyglucose positron emission tomography. J Clin Oncol 2006;24:5366–72.PubMedCrossRef Rousseau C, Devillers A, Sagan C, Ferrer L, Bridji B, Campion L, et al. Monitoring of early response to neoadjuvant chemotherapy in stage II and III breast cancer by [18F]fluorodeoxyglucose positron emission tomography. J Clin Oncol 2006;24:5366–72.PubMedCrossRef
4.
go back to reference Ceresoli GL, Chiti A, Zucali PA, Rodari M, Lutman RF, Salamina S, et al. Early response evaluation in malignant pleural mesothelioma by positron emission tomography with [18F]fluorodeoxyglucose. J Clin Oncol 2006;24:4587–93.PubMedCrossRef Ceresoli GL, Chiti A, Zucali PA, Rodari M, Lutman RF, Salamina S, et al. Early response evaluation in malignant pleural mesothelioma by positron emission tomography with [18F]fluorodeoxyglucose. J Clin Oncol 2006;24:4587–93.PubMedCrossRef
5.
go back to reference Fruchart C, Reman O, Le Stang N, Musafiri D, Cheze S, Macro M, et al. Prognostic value of early 18 fluorodeoxyglucose positron emission tomography and gallium-67 scintigraphy in aggressive lymphoma: a prospective comparative study. Leuk Lymphoma 2006;47:2547–57.PubMedCrossRef Fruchart C, Reman O, Le Stang N, Musafiri D, Cheze S, Macro M, et al. Prognostic value of early 18 fluorodeoxyglucose positron emission tomography and gallium-67 scintigraphy in aggressive lymphoma: a prospective comparative study. Leuk Lymphoma 2006;47:2547–57.PubMedCrossRef
6.
go back to reference Yamane T, Daimaru O, Ito S, Yoshiya K, Nagata T, Ito S, et al. Decreased 18F-FDG uptake 1 day after initiation of chemotherapy for malignant lymphoma. J Nucl Med 2004;45:1838–42.PubMed Yamane T, Daimaru O, Ito S, Yoshiya K, Nagata T, Ito S, et al. Decreased 18F-FDG uptake 1 day after initiation of chemotherapy for malignant lymphoma. J Nucl Med 2004;45:1838–42.PubMed
7.
go back to reference Bokemeyer C, Kollmannsberger C, Oechsle K, Dohmen BM, Pfannenberg A, Claussen CD, et al. Early prediction of treatment response to high-dose salvage chemotherapy in patients with relapsed germ cell cancer using [(18)F]FDG PET. Br J Cancer 2002;86:506–11.PubMedCrossRef Bokemeyer C, Kollmannsberger C, Oechsle K, Dohmen BM, Pfannenberg A, Claussen CD, et al. Early prediction of treatment response to high-dose salvage chemotherapy in patients with relapsed germ cell cancer using [(18)F]FDG PET. Br J Cancer 2002;86:506–11.PubMedCrossRef
8.
go back to reference Pfannenberg AC, Oechsle K, Kollmannsberger C, Dohmen BM, Bokemeyer C, Bares R, et al. Early prediction of treatment response to high-dose chemotherapy in patients with relapsed germ cell tumors using [18F]FDG-PET, CT or MRI, and tumor marker. Rofo 2004;176:76–84.PubMed Pfannenberg AC, Oechsle K, Kollmannsberger C, Dohmen BM, Bokemeyer C, Bares R, et al. Early prediction of treatment response to high-dose chemotherapy in patients with relapsed germ cell tumors using [18F]FDG-PET, CT or MRI, and tumor marker. Rofo 2004;176:76–84.PubMed
9.
go back to reference Leyton J, Latigo JR, Perumal M, Dhaliwal H, He Q, Aboagye EO. 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 2005;65:4202–10.PubMedCrossRef Leyton J, Latigo JR, Perumal M, Dhaliwal H, He Q, Aboagye EO. 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 2005;65:4202–10.PubMedCrossRef
10.
go back to reference Cullinane C, Dorow DS, Kansara M, Conus N, Binns D, Hicks RJ, et al. An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development. Cancer Res 2005;65:9633–36.PubMedCrossRef Cullinane C, Dorow DS, Kansara M, Conus N, Binns D, Hicks RJ, et al. An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development. Cancer Res 2005;65:9633–36.PubMedCrossRef
11.
go back to reference Su H, Bodenstein C, Dumont RA, Seimbille Y, Dubinett S, Phelps ME, et al. Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors. Clin Cancer Res 2006;12:5659–67.PubMedCrossRef Su H, Bodenstein C, Dumont RA, Seimbille Y, Dubinett S, Phelps ME, et al. Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors. Clin Cancer Res 2006;12:5659–67.PubMedCrossRef
12.
go back to reference Hwang RF, Yokoi K, Bucana CD, Tsan R, Killion JJ, Evans DB, et al. Inhibition of platelet-derived growth factor receptor phosphorylation by STI571 (Gleevec) reduces growth and metastasis of human pancreatic carcinoma in an orthotopic nude mouse model. Clin Cancer Res 2003;9:6534–44.PubMed Hwang RF, Yokoi K, Bucana CD, Tsan R, Killion JJ, Evans DB, et al. Inhibition of platelet-derived growth factor receptor phosphorylation by STI571 (Gleevec) reduces growth and metastasis of human pancreatic carcinoma in an orthotopic nude mouse model. Clin Cancer Res 2003;9:6534–44.PubMed
13.
go back to reference Huisman MC, Reder S, Weber AW, Ziegler SI, Schwaiger M. Performance evaluation of the Philips MOSAIC small animal PET scanner. Eur J Nucl Med Mol Imaging 2007;34:532–40.PubMedCrossRef Huisman MC, Reder S, Weber AW, Ziegler SI, Schwaiger M. Performance evaluation of the Philips MOSAIC small animal PET scanner. Eur J Nucl Med Mol Imaging 2007;34:532–40.PubMedCrossRef
14.
go back to reference Chiang S, Cardi C, Matej S, Zhuang H, Newberg A, Alavi A, et al. Clinical validation of fully 3-D versus 2.5-D RAMLA reconstruction on the Philips-ADAC CPET PET scanner. Nucl Med Commun 2004;25:1103–07.PubMedCrossRef Chiang S, Cardi C, Matej S, Zhuang H, Newberg A, Alavi A, et al. Clinical validation of fully 3-D versus 2.5-D RAMLA reconstruction on the Philips-ADAC CPET PET scanner. Nucl Med Commun 2004;25:1103–07.PubMedCrossRef
15.
go back to reference Aide N, Louis MH, Dutoit S, Labiche A, Lemoisson E, Briand M, et al. Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study. Nucl Med Commun 2007;28:813–22.PubMedCrossRef Aide N, Louis MH, Dutoit S, Labiche A, Lemoisson E, Briand M, et al. Improvement of semi-quantitative small-animal PET data with recovery coefficients: a phantom and rat study. Nucl Med Commun 2007;28:813–22.PubMedCrossRef
16.
go back to reference Calvet L, Geoerger B, Regairaz M, Opolon P, Machet L, Morizet J, et al. Pleiotrophin, a candidate gene for poor tumor vasculature and in vivo neuroblastoma sensitivity to irinotecan. Oncogene 2006;25:3150–59.PubMedCrossRef Calvet L, Geoerger B, Regairaz M, Opolon P, Machet L, Morizet J, et al. Pleiotrophin, a candidate gene for poor tumor vasculature and in vivo neuroblastoma sensitivity to irinotecan. Oncogene 2006;25:3150–59.PubMedCrossRef
17.
go back to reference Elie N, Plancoulaine B, Signolle JP, Herlin P. A simple way of quantifying immunostained cell nuclei on the whole histologic section. Cytometry A 2003;56:37–45.PubMedCrossRef Elie N, Plancoulaine B, Signolle JP, Herlin P. A simple way of quantifying immunostained cell nuclei on the whole histologic section. Cytometry A 2003;56:37–45.PubMedCrossRef
18.
go back to reference Elie N, Kaliski A, Peronneau P, Opolon P, Roche A, Lassau N. Methodology for quantifying interactions between perfusion evaluated by DCE-US and hypoxia throughout tumor growth. Ultrasound Med Biol 2007;33:549–60.PubMedCrossRef Elie N, Kaliski A, Peronneau P, Opolon P, Roche A, Lassau N. Methodology for quantifying interactions between perfusion evaluated by DCE-US and hypoxia throughout tumor growth. Ultrasound Med Biol 2007;33:549–60.PubMedCrossRef
19.
go back to reference Galaup A, Cazes A, Le Jan S, Philippe J, Connault E, Le Coz E, et al. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness. Proc Natl Acad Sci U S A 2006;103:18721–26.PubMedCrossRef Galaup A, Cazes A, Le Jan S, Philippe J, Connault E, Le Coz E, et al. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness. Proc Natl Acad Sci U S A 2006;103:18721–26.PubMedCrossRef
20.
go back to reference Aide N, Labiche A, Herlin P, Paciencia M, Poulain L, Dutoit S, et al. Usefulness of automatic quantification of immunochemical staining on whole tumor sections for correlation with oncological small animal pet studies: an example with cell proliferation, glucose transporter 1 and FDG. Mol Imaging Biol 2008;10:237–44.PubMedCrossRef Aide N, Labiche A, Herlin P, Paciencia M, Poulain L, Dutoit S, et al. Usefulness of automatic quantification of immunochemical staining on whole tumor sections for correlation with oncological small animal pet studies: an example with cell proliferation, glucose transporter 1 and FDG. Mol Imaging Biol 2008;10:237–44.PubMedCrossRef
21.
go back to reference Chung JK, Lee YJ, Kim C, Choi SR, Kim M, Lee K, et al. Mechanisms related to [18F]fluorodeoxyglucose uptake of human colon cancers transplanted in nude mice. J Nucl Med 1999;40:339–46.PubMed Chung JK, Lee YJ, Kim C, Choi SR, Kim M, Lee K, et al. Mechanisms related to [18F]fluorodeoxyglucose uptake of human colon cancers transplanted in nude mice. J Nucl Med 1999;40:339–46.PubMed
22.
go back to reference Smith TA. The rate-limiting step for tumor [18F]fluoro-2-deoxy-D-glucose (FDG) incorporation. Nucl Med Biol 2001;28:1–4.PubMedCrossRef Smith TA. The rate-limiting step for tumor [18F]fluoro-2-deoxy-D-glucose (FDG) incorporation. Nucl Med Biol 2001;28:1–4.PubMedCrossRef
23.
go back to reference Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 1992;33:1972–80.PubMed Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 1992;33:1972–80.PubMed
24.
go back to reference Furuta M, Hasegawa M, Hayakawa K, Yamakawa M, Ishikawa H, Nonaka T, et al. Rapid rise in FDG uptake in an irradiated human tumour xenograft. Eur J Nucl Med 1997;24:435–38.PubMed Furuta M, Hasegawa M, Hayakawa K, Yamakawa M, Ishikawa H, Nonaka T, et al. Rapid rise in FDG uptake in an irradiated human tumour xenograft. Eur J Nucl Med 1997;24:435–38.PubMed
25.
go back to reference Aliaga A, Rousseau JA, Cadorette J, Croteau E, van Lier JE, Lecomte R, et al. A small animal positron emission tomography study of the effect of chemotherapy and hormonal therapy on the uptake of 2-deoxy-2-[F-18]fluoro-D-glucose in murine models of breast cancer. Mol Imaging Biol 2007;9:144–50.PubMedCrossRef Aliaga A, Rousseau JA, Cadorette J, Croteau E, van Lier JE, Lecomte R, et al. A small animal positron emission tomography study of the effect of chemotherapy and hormonal therapy on the uptake of 2-deoxy-2-[F-18]fluoro-D-glucose in murine models of breast cancer. Mol Imaging Biol 2007;9:144–50.PubMedCrossRef
26.
go back to reference Dehdashti F, Flanagan FL, Mortimer JE, Katzenellenbogen JA, Welch MJ, Siegel BA. Positron emission tomographic assessment of “metabolic flare” to predict response of metastatic breast cancer to antiestrogen therapy. Eur J Nucl Med 1999;26:51–6.PubMedCrossRef Dehdashti F, Flanagan FL, Mortimer JE, Katzenellenbogen JA, Welch MJ, Siegel BA. Positron emission tomographic assessment of “metabolic flare” to predict response of metastatic breast cancer to antiestrogen therapy. Eur J Nucl Med 1999;26:51–6.PubMedCrossRef
27.
go back to reference Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 2001;19:2797–03.PubMed Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 2001;19:2797–03.PubMed
28.
go back to reference Fishel ML, He Y, Reed AM, Chin-Sinex H, Hutchins GD, Mendonca MS, et al. Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth. DNA Repair (Amst) 2008;7:177–86.CrossRef Fishel ML, He Y, Reed AM, Chin-Sinex H, Hutchins GD, Mendonca MS, et al. Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth. DNA Repair (Amst) 2008;7:177–86.CrossRef
29.
go back to reference Haberkorn U, Bellemann ME, Brix G, Kamencic H, Morr I, Traut U, et al. Apoptosis and changes in glucose transport early after treatment of Morris hepatoma with gemcitabine. Eur J Nucl Med 2001;28:418–25.PubMedCrossRef Haberkorn U, Bellemann ME, Brix G, Kamencic H, Morr I, Traut U, et al. Apoptosis and changes in glucose transport early after treatment of Morris hepatoma with gemcitabine. Eur J Nucl Med 2001;28:418–25.PubMedCrossRef
30.
go back to reference Nanni C, Di Leo K, Tonelli R, Pettinato C, Rubello D, Spinelli A, et al. FDG small animal PET permits early detection of malignant cells in a xenograft murine model. Eur J Nucl Med Mol Imaging 2007;34:755–62.PubMedCrossRef Nanni C, Di Leo K, Tonelli R, Pettinato C, Rubello D, Spinelli A, et al. FDG small animal PET permits early detection of malignant cells in a xenograft murine model. Eur J Nucl Med Mol Imaging 2007;34:755–62.PubMedCrossRef
31.
go back to reference Macheda ML, Rogers S, Best JD. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 2005;202:654–62.PubMedCrossRef Macheda ML, Rogers S, Best JD. Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 2005;202:654–62.PubMedCrossRef
32.
go back to reference Friberg S, Mattson S. On the growth rates of human malignant tumors: implications for medical decision making. J Surg Oncol 1997;65:284–97.PubMedCrossRef Friberg S, Mattson S. On the growth rates of human malignant tumors: implications for medical decision making. J Surg Oncol 1997;65:284–97.PubMedCrossRef
Metadata
Title
Early evaluation of the effects of chemotherapy with longitudinal FDG small-animal PET in human testicular cancer xenografts: early flare response does not reflect refractory disease
Authors
Nicolas Aide
Laurent Poulain
Mélanie Briand
Soizic Dutoit
Stéphane Allouche
Alexandre Labiche
Aurélie Ngo-Van Do
Valérie Nataf
Alain Batalla
Pascal Gauduchon
Jean-noël Talbot
Françoise Montravers
Publication date
01-03-2009
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-008-0984-x

Other articles of this Issue 3/2009

European Journal of Nuclear Medicine and Molecular Imaging 3/2009 Go to the issue