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

Robert E. Lenkinski, Muneeb Ahmed, Atif Zaheer, John V. Frangioni, S. Nahum Goldberg

Research output: Contribution to journalArticle

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 μ 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.

Original languageEnglish (US)
Pages (from-to)1159-1164
Number of pages6
JournalAcademic Radiology
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

Fingerprint

Calcinosis
Optical Imaging
Animal Models
Breast Neoplasms
Durapatite
Contrast Media
Neoplasms
Calcium Oxalate
Breast
Fluorescence
Optical Devices
Inbred F344 Rats
Diphosphonates
Fluorescent Dyes
Needles
Adipose Tissue
Adenocarcinoma
Magnetic Resonance Imaging
Cell Line
Growth

Keywords

  • Breast cancer
  • Hydroxyapatite
  • Microcalcification
  • Near-infrared fluorescence

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Near-infrared fluorescence imaging of microcalcification in an animal model of breast cancer. / Lenkinski, Robert E.; Ahmed, Muneeb; Zaheer, Atif; Frangioni, John V.; Goldberg, S. Nahum.

In: Academic Radiology, Vol. 10, No. 10, 01.10.2003, p. 1159-1164.

Research output: Contribution to journalArticle

Lenkinski, Robert E. ; Ahmed, Muneeb ; Zaheer, Atif ; Frangioni, John V. ; Goldberg, S. Nahum. / Near-infrared fluorescence imaging of microcalcification in an animal model of breast cancer. In: Academic Radiology. 2003 ; Vol. 10, No. 10. pp. 1159-1164.
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N2 - 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 μ 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.

AB - 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 μ 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.

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