Near-infrared fluorescence imaging of microcalcification in an animal model of breast cancer.
OBJECTIVE
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 microm 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.
Lenkinski
Robert E
RE
Department of Radiology, Molecular Imaging Center, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Deaconess Road, Boston, MA 02215, USA.
Ahmed
Muneeb
M
Zaheer
Atif
A
Frangioni
John V
JV
Goldberg
S Nahum
SN
D000818:Animals; D002114:Calcinosis / Q000175:diagnosis*; D002129:Calcium Oxalate / Q000008:administration & dosage; D017886:Durapatite / Q000008:administration & dosage; D005260:Female; D005456:Fluorescent Dyes; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis* / Q000473:pathology; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D013050:Spectrometry, Fluorescence; D019265:Spectroscopy, Near-Infrared
D005456:Fluorescent Dyes; D002129:Calcium Oxalate; D017886:Durapatite