Imaging Cancer in Mice by PET, CT, and Combined PET‐CT

Francisca Mulero1, Luis E. Donate1, Manuel Serrano1

1 Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Publication Name:  Current Protocols in Mouse Biology
Unit Number:   
DOI:  10.1002/9780470942390.mo100137
Online Posting Date:  March, 2011
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The possibility of imaging tumors in live mice has opened new opportunities for cancer research, particularly regarding the ability to perform longitudinal studies in combination with a therapeutic intervention. Here, we detail methods to optimize visualization of murine tumors by positron emission tomography (PET), computed tomography (CT), and combined PET‐CT. Curr. Protoc. Mouse Biol. 1:85‐103. © 2011 by John Wiley & Sons, Inc.

Keywords: cancer; mouse models; positron electron tomography; computed tomography

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Table of Contents

  • Introduction
  • Basic Protocol 1: Imaging by Positron Emission Tomography (PET)
  • Basic Protocol 2: Imaging by Computed Tomography (CT)
  • Basic Protocol 3: Imaging by Multimodality (PET‐CT)
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
  • Tables
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Basic Protocol 1: Imaging by Positron Emission Tomography (PET)

  • Genetically modified mouse models bearing spontaneous tumors in any body location
  • Special mouse diets as necessary
  • Diazepam (5 mg/ml in flip‐top vial; see recipe)
  • Isoflurane
  • Oxygen
  • [18F]FDG (0.01 to 0.1 µg/ mCi), delivered daily from a local cyclotron (e.g., 40 mCi of [18F]FDG of 95% to 99% radiochemical purity in 1 ml of physiological saline solution buffered at pH 6.0, for ∼10 PET scans)
  • Physiological saline: 0.9% (w/v) NaCl
  • Lacryvisc Gel 10 G (3 mg/ml carbomere in benzalconium chloride, commercially available from Alcon,
  • Infrared heating lamp
  • Isoflurane/oxygen‐based anesthesia system fitted with an induction chamber and inhalation masks for mice
  • Dose calibrator (also known as activimeter): e.g., VDC‐505 dose calibrator from Veenstra Instruments (
  • PET‐CT imaging system: e.g., eXplore Vista PET‐CT, GE Healthcare (Fig. A); Argus PET‐CT, SEDECAL (
  • 1‐cc tuberculin syringes
  • 30‐G needles
  • Heating pads: e.g., Gaymar Mul‐T‐Pads (
  • Heating pump to maintain temperature of heating pads: e.g., Gaymar TP600 (
  • eXplore Vista PET‐CT MMWKS software for image acquisition, processing, and analysis
  • Workstation (e.g., Dell PowerEdge) for image acquisition, processing, and analysis meeting the following specifications:
    • PE1950 Xeon 5120 1.86 GHz/4 MB 1066 FSB processor
    • PE1950 PCIX Riser (2 slots)
    • PE1950 Bezel Assembly
    • 2 GB FB 667 MHz Memory (2 × 1 GB dual rank DIMMs)
  • Dell Studio XPS Desktop 435 MT PC (for 3DOSEM image reconstruction) meeting the following specifications:
    • Processor: Intel Core i7 Quad CPU 940 4 × 2.93 GHz
    • Memory: 6144 MB (6 × 1024) 1067 MHZ DDR3
    • Graphics: ATI Radeon HD 3450 256 Mb GDDR2

Basic Protocol 2: Imaging by Computed Tomography (CT)

  • Computed tomography system (e.g., CT Locus from GE Healthcare or CT eXplore Vista from GE Healthcare)
  • eXplore Vista PET‐CT MMWKS software for image acquisition, processing and analysis (incorporating a modified version of the FDK algorithm for CT reconstruction); or Microview for Locus CT for image analysis
  • Additional reagents and equipment for imaging by PET ( protocol 1)

Basic Protocol 3: Imaging by Multimodality (PET‐CT)

  • PET‐CT imaging system (e.g., eXplore Vista PET‐CT, GE Healthcare; Fig. A)
  • Additional reagents and equipment for PET ( protocol 1) and imaging by computed tomography ( protocol 2)
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Literature Cited

   Abbey, C.K., Borowsky, A.D., McGoldrick, E.T., Gregg, J.P., Maglione, J.E., Cardiff, R.D., and Cherry, S.R. 2004. In vivo positron‐emission tomography imaging of progression and transformation in a mouse model of mammary neoplasia. Proc. Natl. Acad. Sci. U.S.A. 101:11438‐11443.
   Berger, F., Lee, Y.‐P., Loening, A.M., Chatziioannou, A., Freedland, S.J., Leahy, R., Lieberman, J.R., Belldegrun, A.S., Sawyers, C.L., and Gambhir, S.S. 2002. Whole‐body skeletal imaging in mice utilizing microPET: Optimization of reproducibility and applications in animal models of bone disease. Eur. J. Nucl. Med. Mol. Imaging 29:1225‐1236.
   Cohade, C., Mourtzidos, K.A., and Wahl, R.L. 2003. “USA fat”: Prevalence is related to ambient outdoor temperature evaluation with 18F‐FDG PET/CT. J. Nucl. Med. 44:1267‐1270.
   Dearling, J.L., Flynn, A.A., Sutcliffe‐Goulden, J., Petrie, I.A., Boden, R., Green, A.J., Boxer, G.M., Begent, R.H., and Pedley, R.B. 2004. Analysis of the regional uptake of radiolabeled deoxyglucose analogs in human tumor xenografts. J. Nucl. Med. 45:101‐107.
   Dendy, P. and Heaton, B. 1999. Tomographic imaging. In Physics for Diagnostic Radiology (P. Dendy and B. Heaton, eds.) pp. 249‐278. Institute of Physics, Bristol, U.K.
   Dilmanian, F.A., Wu, X.Y., Parsons, E.C., Ren, B., Kress, J., Button, T.M., Chapman, L.D., Coderre, J.A., Giron, F., Greenberg, D., Krus, D.J., Liang, Z., Marcovici, S,, Petersen, M.J., Roque, C.T., Shleifer, M., Slatkin, D.N., Thomlinson, W.C., Yamamoto, K., and Zhong, Z. 1997. Single‐ and dual‐energy CT with monochromatic synchrotron X‐rays. Phys. Med. Biol. 42:371‐387.
   Fueger, B.J., Czernin, J., Hildebrandt, I., Tran, C., Halpern, B., Stout, D., Phelps, M.E., and Weber, W.A. 2006. Impact of animal handling on the results of 18F‐FDG PET studies in mice. J. Nucl. Med. 47:999‐1006.
   Gambhir, S.S. 2002. Molecular imaging of cancer with positron emission tomography. Nat. Rev. Cancer 2:683‐693.
   Holdsworth, D.W. and Thornton, M.M. 2002. Micro‐CT in small animal and specimen imaging. Trends Biotechnol. 20:S34‐S39.
   Massoud, T.F. and Gambhir, S.S. 2003. Molecular imaging in living subjects: Seeing fundamental biological processes in a new light. Genes Dev. 17:545‐580
   Pascau J., Vaquero, J.J., Abella, M., Cacho, R., Lage, E., and Desco, M. 2006. Multimodality workstation for small animal image visualization and analysis. Mol. Imaging Biol. 8:97‐98.
   Paulus, M.J., Gleason, S.S., Easterly, M.E., and Foltz, C.J. 2001. A review of high‐resolution X‐ray computed tomography and other imaging modalities for small animal research. Lab. Anim. (NY) 30:36‐45.
   Schelbert, H.R. 1998. The usefulness of positron emission tomography. Curr. Probl. Cardiol. 23:69‐120.
   Strijckmans, K. 2001. The isochronous cyclotron: Principles and recent developments. Comput. Med. Imaging Graph. 25:69‐78.
   Toyama, H., Ichise, M, Liow, J.S., Vines, D.C., Seneca, N.M., Modell, K.J., Seidel, J., Green, M.V., and Innis, R.B. 2004. Evaluation of anaesthesia effects on 18F‐FDG uptake in mouse brain and heart using small animal PET. Nucl. Med. Biol. 31:251‐256.
   Vaquero, J.J., Redondo, S., Lage, E., Abella, M., Sisniega, A., Tapias, G., and Desco M. 2008. Assessment of a new high‐performance small‐animal X‐ray tomography. IEEE Trans. Nucl. Sci. 55:898‐905.
   Wahl, R., Henry, C.A., and Ethier, S.P. 1992. Serum glucose: Effects on tumor and normal tissue accumulation of 2‐[F‐18)]‐fluoro‐2‐deoxy‐D‐glucose in rodents with mammary carcinoma. Radiology 183:643‐647.
   Wang, Y., Seidel, J., Tsui, W., Vaquero, J.J., and Pomper, M.G. 2006. Performance evaluation of the GE Healthcare eXplore VISTA dual‐ring small‐animal PET Scanner. J. Nucl. Med. 47:1891‐1900.
Internet Resources
  General Electric Triumph Tri‐modality PET/SPECT/CT.
  SEDECAL Argus PET‐CT.∼q_catalogId∼e_‐11∼a_categoryId∼e_1029715∼a_catTree∼e_100010,1007660,1011525,1029715∼a_langId∼e_‐11∼a_storeId∼e_10001.htm
  Siemens Inveon PET & Inveon CT.
  Philips Mosaic HP PET.
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