Skip to main content

Advertisement

SpringerLink
Log in

High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The objective of the study was to evaluate state-of-the-art clinical PET/CT technology in performing static and dynamic imaging of several mice simultaneously.

Methods

A mouse-sized phantom was imaged mimicking simultaneous imaging of three mice with computation of recovery coefficients (RCs) and spillover ratios (SORs). Fifteen mice harbouring abdominal or subcutaneous tumours were imaged on clinical PET/CT with point spread function (PSF) reconstruction after injection of [18F]fluorodeoxyglucose or [18F]fluorothymidine. Three of these mice were imaged alone and simultaneously at radial positions –5, 0 and 5 cm. The remaining 12 tumour-bearing mice were imaged in groups of 3 to establish the quantitative accuracy of PET data using ex vivo gamma counting as the reference. Finally, a dynamic scan was performed in three mice simultaneously after the injection of 68Ga-ethylenediaminetetraacetic acid (EDTA).

Results

For typical lesion sizes of 7–8 mm phantom experiments indicated RCs of 0.42 and 0.76 for ordered subsets expectation maximization (OSEM) and PSF reconstruction, respectively. For PSF reconstruction, SORair and SORwater were 5.3 and 7.5%, respectively. A strong correlation (r 2 = 0.97, p < 0.0001) between quantitative data obtained in mice imaged alone and simultaneously in a group of three was found following PSF reconstruction. The correlation between ex vivo counting and PET/CT data was better with PSF reconstruction (r 2 = 0.98; slope = 0.89, p < 0.0001) than without (r 2 = 0.96; slope = 0.62, p < 0.001). Valid time-activity curves of the blood pool, kidneys and bladder could be derived from 68Ga-EDTA dynamic acquisition.

Conclusion

New generation clinical PET/CT can be used for simultaneous imaging of multiple small animals in experiments requiring high throughput and where a dedicated small animal PET system is not available.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. 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.

    Article  PubMed  Google Scholar 

  2. Aide N, Poulain L, Briand M, Dutoit S, Allouche S, Labiche A, et al. 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. Eur J Nucl Med Mol Imaging 2009;36:396–405.

    Article  CAS  PubMed  Google Scholar 

  3. Dorow DS, Cullinane C, Conus N, Roselt P, Binns D, McCarthy TJ, et al. Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033. Eur J Nucl Med Mol Imaging 2006;33:441–52.

    Article  PubMed  Google Scholar 

  4. Wolf G, Abolmaali N. Imaging tumour-bearing animals using clinical scanners. Int J Radiat Biol 2009;85:752–62.

    Article  CAS  PubMed  Google Scholar 

  5. Panin VY, Kehren F, Michel C, Casey M. Fully 3-D PET reconstruction with system matrix derived from point source measurements. IEEE Trans Med Imaging 2006;25:907–21.

    Article  PubMed  Google Scholar 

  6. Pichler BJ, Wehrl HF, Judenhofer MS. Latest advances in molecular imaging instrumentation. J Nucl Med 2008;49(Suppl 2):5S–23S.

    Article  PubMed  Google Scholar 

  7. Townsend DW. Dual-modality imaging: combining anatomy and function. J Nucl Med 2008;49:938–55.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. Tatsumi M, Nakamoto Y, Traughber B, Marshall LT, Geschwind JF, Wahl RL. Initial experience in small animal tumor imaging with a clinical positron emission tomography/computed tomography scanner using 2-[F-18]fluoro-2-deoxy-D-glucose. Cancer Res 2003;63:6252–7.

    CAS  PubMed  Google Scholar 

  10. Visser EP, Van Dalen JA, Laverman P, Newport D, Corstens FHM, Oyen WJG, et al. Evaluation of attenuation correction in the Inveon preclinical PET scanner using two opposite, rotating 57-Co sources. Eur J Nucl Med Mol Imaging 2007;34:S227.

    Google Scholar 

  11. Machulla HJ, Blocher A, Kuntzsch M, Piert M, Wei R, Grierson JR. Simplified labeling approach for synthesizing 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT). J Radioanal Nucl Chem 2000;243:843–46.

    Article  CAS  Google Scholar 

  12. Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, et al. Processing of generator-produced 68Ga for medical application. J Nucl Med 2007;48:1741–8.

    Article  CAS  PubMed  Google Scholar 

  13. Brambilla M, Secco C, Dominietto M, Matheoud R, Sachetti G, Inglese E. Performance characteristics obtained for a new 3-dimensional lutetium oxyorthosilicate-based whole-body PET/CT scanner with the National Electrical Manufacturers Association NU 2–2001 standard. J Nucl Med 2005;46:2083–91.

    CAS  PubMed  Google Scholar 

  14. Daube-Witherspoon ME, Karp JS, Casey ME, DiFillipo FP, Hines H, Muehllehner G, et al. PET performance measurements using the NEMA NU-2001 standard. J Nucl Med 2002;43:1398–409.

    PubMed  Google Scholar 

  15. Watson CC. New, faster, image-based scatter correction for 3-D PET. IEEE Trans Nucl Sci 2000;47:1587–94.

    Article  Google Scholar 

  16. Kinahan PE, Hasegawa BH, Beyer T. X-ray-based attenuation correction for positron emission tomography/computed tomography scanners. Semin Nucl Med 2003;33:166–79.

    Article  PubMed  Google Scholar 

  17. Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T. Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 2005;11:63–70.

    Article  CAS  PubMed  Google Scholar 

  18. Hoffman EJ, Huang SC, Phelps ME. Quantitation in positron emission computed tomography: 1. Effect of object size. J Comput Assist Tomogr 1979;3:299–308.

    Article  CAS  PubMed  Google Scholar 

  19. Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med 2007;48:932–45.

    Article  PubMed  Google Scholar 

  20. 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.

    Article  PubMed  Google Scholar 

  21. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–10.

    CAS  PubMed  Google Scholar 

  22. Hilson A. Bland-Altman plot. Radiology 2004;231:604. author reply 604–5.

    Article  PubMed  Google Scholar 

  23. Dandekar M, Tseng JR, Gambhir SS. Reproducibility of 18F-FDG microPET studies in mouse tumor xenografts. J Nucl Med 2007;48:602–7.

    Article  PubMed  Google Scholar 

  24. Nagengast WB, de Vries EG, Hospers GA, Mulder NH, de Jong JR, Hollema H, et al. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J Nucl Med 2007;48:1313–9.

    Article  CAS  PubMed  Google Scholar 

  25. Brix G, Doll J, Belleman ME, Trojan H, Haberkorn U, Schmidlin P, et al. Use of scanner characteristics in iterative image reconstruction for high-resolution positron emission tomography studies of small animals. Eur J Nucl Med 1997;24:779–86.

    CAS  PubMed  Google Scholar 

  26. Seemann MD, Beck R, Ziegler S. In vivo tumor imaging using a state-of-the-art clinical PET/CT in comparison with a small animal PET and a small animal CT. Technol Cancer Res Treat 2006;5:537–42.

    PubMed  Google Scholar 

  27. Aubry K, Shao Z, Monteil J, Paraf F, Bessède JP, Rigaud M. FDG-PET/CT of head and neck squamous cell carcinoma in a rat model. Mol Imaging Biol 2009;11:88–93.

    Article  PubMed  Google Scholar 

  28. Song SL, Liu JJ, Huang G, Wang ZH, Song YY, Sun XG, et al. Changes in 18F-FDG uptake within minutes after chemotherapy in a rabbit VX2 tumor model. J Nucl Med 2008;49:303–9.

    Article  PubMed  Google Scholar 

  29. Willekens I, Lahoutte T, Buls N, Vanhove C, Deklerck R, Bossuyt A, et al. Time-course of contrast enhancement in spleen and liver with Exia 160, Fenestra LC, and VC. Mol Imaging Biol 2009;11:128–35.

    Article  PubMed  Google Scholar 

  30. Aide N, Kinross K, Neels O, Roselt P, Hicks RJ. A dual contrast agent protocol improves 18F-FDG and 18F-FLT PET/CT imaging of mice bearing abdominal tumours. Eur J Nucl Med Mol Imaging 2009;36:S415.

    Article  CAS  Google Scholar 

  31. Boone JM, Velazquez O, Cherry SR. Small-animal X-ray dose from micro-CT. Mol Imaging 2004;3:149–58.

    Article  PubMed  Google Scholar 

  32. Winkelmann CT, Figueroa SD, Rold TL, Volkert WA, Hoffman TJ. Microimaging characterization of a B16–F10 melanoma metastasis mouse model. Mol Imaging 2006;5:105–14.

    PubMed  Google Scholar 

  33. Bao Q, Newport D, Chen M, Stout DB, Chatziioannou AF. Performance evaluation of the Inveon dedicated PET preclinical tomograph based on the NEMA NU-4 standards. J Nucl Med 2009;50:401–8.

    Article  PubMed  Google Scholar 

  34. Constantinescu CC, Mukherjee J. Performance evaluation of an Inveon PET preclinical scanner. Phys Med Biol 2009;54:2885–99.

    Article  PubMed  Google Scholar 

  35. Visser EP, Disselhorst JA, Brom M, Laverman P, Gotthardt M, Oyen WJ, et al. Spatial resolution and sensitivity of the Inveon small-animal PET scanner. J Nucl Med 2009;50:139–47.

    Article  PubMed  Google Scholar 

  36. Wang Y, Seidel J, Tsui BM, Vaquero JJ, Pomper MG. Performance evaluation of the GE Healthcare eXplore VISTA dual-ring small-animal PET scanner. J Nucl Med 2006;47:1891–900.

    PubMed  Google Scholar 

  37. Qi J, Leahy RM, Cherry SR, Chatziioannou AF, Farquhar T. High-resolution 3D Bayesian image reconstruction using the microPET small-animal scanner. Phys Med Biol 1998;43:1001–13.

    Article  CAS  PubMed  Google Scholar 

  38. Sureau FC, Reader AJ, Comtat C, Leroy C, Ribeiro MJ, Buvat I, et al. Impact of image-space resolution modeling for studies with the high-resolution research tomograph. J Nucl Med 2008;49:1000–8.

    Article  PubMed  Google Scholar 

  39. Varrone A, Sjöholm N, Eriksson L, Gulyás B, Halldin C, Farde L. Advancement in PET quantification using 3D-OP-OSEM point spread function reconstruction with the HRRT. Eur J Nucl Med Mol Imaging 2009;36:1639–50.

    Article  PubMed  Google Scholar 

  40. Cheng TE, Yoder KK, Normandin MD, Risacher SL, Converse AK, Hampel JA, et al. A rat head holder for simultaneous scanning of two rats in small animal PET scanners: design, construction, feasibility testing and kinetic validation. J Neurosci Methods 2009;176:24–33.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the French Ligue contre le cancer, comité du calvados and by a Fellowship from the Fondation de France.

The authors are indebted to Emily Hong, Jason Callahan, David Binns and Mark Scalzo for their help during animal PET acquisitions and ex vivo counting, and to the animal technologists and research assistants (Rachel Walker, Susan Jackson, Kerry Ardley, Jeannette Valentan, Ekaterina Bogatyreva and Laura Kirby) from the Centre for Molecular Imaging for animal care and tracer injections. Dr. Aide thanks Dr. Lerouge for her continuous support during this work.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Bioticla Team, EA1792, IFR 146 ICORE, GRECAN, François Baclesse Cancer Centre and Caen University, Caen, France

    Nicolas Aide

  2. PET Unit, Caen University Hospital and François Baclesse Cancer Centre, Caen, France

    Nicolas Aide, Cédric Desmonts, Denis Agostini, Stéphane Bardet & Gérard Bouvard

  3. Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne, Australia

    Nicolas Aide, Jean-Mathieu Beauregard, Kathryn Kinross, Peter Roselt, Oliver Neels & Rodney J. Hicks

  4. cmi-experts GmbH, Zurich, Switzerland

    Thomas Beyer

  5. Department of Nuclear Medicine, University Hospital Essen, Essen, Germany

    Thomas Beyer

  6. Institute of Nuclear Medicine, University Hospital Bern, Bern, Switzerland

    Thomas Beyer

  7. Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Australia

    Kathryn Kinross

  8. The Department of Medicine, University of Melbourne, Parkville, Australia

    Rodney J. Hicks

  9. Nuclear Medicine Department, Centre François Baclesse, Avenue Général Harris, 14076, Caen cedex 5, France

    Nicolas Aide

Authors
  1. Nicolas Aide
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cédric Desmonts
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jean-Mathieu Beauregard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas Beyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kathryn Kinross
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter Roselt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Oliver Neels
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Denis Agostini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stéphane Bardet
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gérard Bouvard
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Rodney J. Hicks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicolas Aide.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aide, N., Desmonts, C., Beauregard, JM. et al. High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications. Eur J Nucl Med Mol Imaging 37, 991–1001 (2010). https://doi.org/10.1007/s00259-009-1352-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-009-1352-1

Keywords

Search

Navigation