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Breast cancer metastasis to bone: evaluation of bioluminescent imaging and microSPECT/CT for detecting bone metastasis in immunodeficient mice

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Abstract

This study sought to determine if weekly X-ray exposure affected breast cancer cell metastasis to bone and to also evaluate the use of bioluminescent imaging (BLI) and microSPECT for detection of metastatic bone lesions. Five week old nude mice were randomly assigned to the CT exposed (n = 7) and no CT exposure (n = 6) treatment groups. Mice received an intracardiac injection of MDA-MB-435 human breast cancer cells transduced with luciferase, or a sham injection (saline). The CT exposed group of mice received CT irradiation once a week for 5 weeks. All mice underwent weekly BLI and select mice received Tc-99m-MDP followed by microSPECT imaging after 5 weeks. Pathological evaluation and histomorphometry were used to assess the affect of CT X-rays on bone metastasis and to evaluate BLI. BLI results found no significant difference in metastasis between animals that received CT and those that did not (P > 0.05); however, histomorphometry of the knee joints revealed a significant increase (P = 0.029) in tumor area of the leg bones in mice that received CT exposure (60% ± 7%) compared to animals that did not receive CT scans (33% ± 8%). Compared to histological analysis, BLI of the leg and spine was determined to have excellent sensitivity (100%), good specificity (80–90%) and accuracy (90–96%), a positive predictive value of 81–93% and a 100% negative predictive value. Thus, multi-modality imaging techniques can be very useful for monitoring bone metastasis, however microCT X-rays should be used judiciously in order to limit irradiation that may stimulate increased metastasis to specific regions of the skeleton. MicroSPECT imaging did not detect metastatic lesions in the legs of these young nude mice.

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Acknowledgments

We are indebted to the superb technical assistance from Dr. Arig Ibrahim Hashim, as well as Patty Lott and Dezhi Wang at the University of Alabama at Birmingham Center for Metabolic Bone Disease Histomorphometry Core Facility, P30AR046031. This project was made possible by Grant Number R21AT01636 to R.W.H. from the National Center for Complementary and Alternative Medicine (NCCAM). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, or the National Institutes of Health. This study was also supported by the National Institutes of Health grants, T32AR047512 to S.C., RO1-CA108585, RO1-CA93796 to G.P.S. and 5P30CA013148-35, Small Animal Imaging Shared Facility to K.R.Z.

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Authors and Affiliations

  1. Department of Pathology, University of Alabama at Birmingham, 701 South 19th Street, LHRB Room 531, Birmingham, Alabama, 35294, USA

    S. Cowey, A. A. Szafran, G. P. Siegal, R. A. Desmond & R. W. Hardy

  2. Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA

    K. R. Zinn & H. Kim

  3. Mucosal HIV and Immunology Center, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA

    J. Kappes

  4. Departments of Cell Biology and Surgery, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA

    G. P. Siegal

  5. Center for Metabolic Bone Disease, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA

    S. Cowey, G. P. Siegal & R. W. Hardy

  6. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA

    G. P. Siegal & R. W. Hardy

  7. Department of Physiology, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA

    L. Evans

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  1. S. Cowey
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  2. A. A. Szafran
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  3. J. Kappes
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  4. K. R. Zinn
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  5. G. P. Siegal
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  6. R. A. Desmond
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  7. H. Kim
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  8. L. Evans
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  9. R. W. Hardy
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Correspondence to R. W. Hardy.

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Cowey, S., Szafran, A.A., Kappes, J. et al. Breast cancer metastasis to bone: evaluation of bioluminescent imaging and microSPECT/CT for detecting bone metastasis in immunodeficient mice. Clin Exp Metastasis 24, 389–401 (2007). https://doi.org/10.1007/s10585-007-9076-8

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  • DOI: https://doi.org/10.1007/s10585-007-9076-8

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