Academic Radiology
Volume 10, Issue 10 , Pages 1159-1164, October 2003

Near-infrared fluorescence imaging of microcalcification in an animal model of breast cancer1☆

  • Robert E Lenkinski, PhD

      Affiliations

    • Departments of Radiology, USA
    • Molecular Imaging Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Road, Boston, MA 02215, USA
    • Corresponding Author InformationAddress correspondence to R.E.L., PhD, Department of Radiology, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston MA 02215, USA
    • ,
  • Muneeb Ahmed, MD

      Affiliations

    • Departments of Radiology, USA
    • Molecular Imaging Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Road, Boston, MA 02215, USA
    • ,
  • Atif Zaheer, MD

      Affiliations

    • Departments of Radiology, USA
    • Molecular Imaging Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Road, Boston, MA 02215, USA
    • ,
  • John V Frangioni, MD, PhD

      Affiliations

    • Departments of Radiology, USA
    • Department of Medicine (Division of Hematology and Oncology), USA
    • Molecular Imaging Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Road, Boston, MA 02215, USA
    • ,
  • S.Nahum Goldberg, MD

      Affiliations

    • Departments of Radiology, USA
    • Molecular Imaging Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Road, Boston, MA 02215, USA

Received 9 June 2003; accepted 24 June 2003.

Abstract 

Rationale and Objectives. At present, there is no animal model of breast cancer that forms reproducible microcalcification. The aim of this study was to develop a straightforward, reproducible model system that could be used to develop multimodality contrast agents for the identification of breast cancer microcalcification.

Methods. The R3230 mammary adenocarcinoma cell line was implanted in the mammary fat pad of female Fischer 344 rats (two rats with two implanted tumors and two rats with a single implanted tumor). After growth to 1–2 cm in diameter, tumors were implanted with 100 μm hydroxyapatite crystals (positive control) or calcium oxalate crystals (negative control). Twenty-four hours after crystal implantation, rats were injected intravenously with a previously described near-infrared fluorescent bisphosphonate derivative known as Pam78, and the tumors were imaged using a reflectance optical imaging system.

Results. Tumors implanted with hydroxyapatite displayed bright, focal, near-infrared fluorescence in the area of crystal implantation. Control tumors, grown in the same animal and implanted with calcium oxalate, did not display any near-infrared fluorescence, even along the needle track used for crystal implantation.

Conclusions. A simple and rapid animal model of focal calcification in breast cancer tumors has been developed and validated. The model used Pam78, a near-infrared fluorescent contrast agent specific for hydroxyapatite. The potential usefulness of the model for developing similar contrast agents for magnetic resonance and other imaging modalities is discussed.

Keywords:  Near-infrared fluorescence, breast cancer, microcalcification, hydroxyapatite

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☆ This work was funded by National Institutes of Health grant no. CA-70362 (R.E.L.) and Department of Energy (Office of Biological and Environmental Research) grant no. DE-FG02-01ER63188 (J.V.F.).

PII: S1076-6332(03)00253-8

doi:10.1016/S1076-6332(03)00253-8

Academic Radiology
Volume 10, Issue 10 , Pages 1159-1164, October 2003

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