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MRI Detection of Early Bone Metastases in B16 Mouse Melanoma Models

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Abstract

Bone metastasis causes significant morbidity in cancer patients, including bone pain, pathologic fractures, nerve compression syndrome, and hypercalcemia. Animal models are utilized to study the pathogenesis of skeletal metastases and to evaluate potential therapeutic agents. Previously published methods for imaging bone metastasis in rodent models have focused on identifying advanced stage metastasis using simple X-rays. Here we report MRI as a method for detecting early bone metastases in mouse models in vivo. B16 mouse melanoma cells were injected into the left cardiac ventricle of C57BL/6 mice and magnetic resonance (MR) images were obtained of the left leg following the development of metastatic disease, when tumor associated bone destruction was histologically present but not visible by X-ray. T1 and T2 relaxation times of bone marrow were measured in healthy control mice and B16 melanoma tumor-bearing mice. Mean T2 values for normal marrow were 28 ms (SD 5) and for diseased bone marrow were 41 ms (SD 3). T2 relaxation time of diseased bone marrow is significantly longer than that of normal bone marrow (P < 0.0001) and can be used as a marker of early bone metastases. These studies demonstrate that MR imaging can detect bone marrow metastases in small animals prior to development of cortical bone loss identified by X-ray.

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Abbreviations

DMEM:

Dulbecco’s Modification of Eagle’s Medium

FOV:

field of view

Gd-DTPA:

gadolinium diethylenetriamine pentaacetic acid, standard MRI contrast agent

GE:

gradient echo

H&E:

hematoxylin and eosin

MR:

magnetic resonance

MRI:

magnetic resonance imaging

NMR:

nuclear magnetic resonance

ROI:

region of interest

SD:

standard deviation

SE:

spin echo

TE:

echo time, imaging parameter

TR:

time to relaxation, imaging parameter

TRAP:

tartrate resistant acid phosphatse, histological stain to identify activated osteoclasts

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Authors and Affiliations

  1. MD, Instructor, Department of Pediatrics, Division of Hematology/Oncology, Washington University School of Medicine, One Children’s Place, Box 8116, St. Louis, MO, 63110, USA

    Karen M. Gauvain

  2. The Alvin J. Siteman Cancer Center, Division of Oncology, Washington University School of Medicine, One Children’s Place, Box 8116, St. Louis, MO, 63110, USA

    Karen M. Gauvain, Joel R. Garbow, Sheng-Kwei Song & Katherine Weilbaecher

  3. Department of Chemistry Division of Oncology, Washington University School of Medicine, One Children’s Place, Box 8116, St. Louis, MO, 63110, USA

    Joel R. Garbow

  4. Department of Radiology Division of Oncology, Washington University School of Medicine, One Children’s Place, Box 8116, St. Louis, MO, 63110, USA

    Joel R. Garbow & Sheng-Kwei Song

  5. Department of Molecular Oncology Division of Oncology, Washington University School of Medicine, One Children’s Place, Box 8116, St. Louis, MO, 63110, USA

    Angela C. Hirbe

  6. Department of Internal Medicine Division of Oncology, Washington University School of Medicine, , One Children’s Place, Box 8116, 63110, St. Louis, Missouri, USA

    Katherine Weilbaecher

Authors
  1. Karen M. Gauvain
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  2. Joel R. Garbow
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  4. Angela C. Hirbe
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  5. Katherine Weilbaecher
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Correspondence to Karen M. Gauvain.

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Gauvain, K.M., Garbow, J.R., Song, SK. et al. MRI Detection of Early Bone Metastases in B16 Mouse Melanoma Models. Clin Exp Metastasis 22, 403–411 (2005). https://doi.org/10.1007/s10585-005-1264-9

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  • DOI: https://doi.org/10.1007/s10585-005-1264-9

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