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on February 16, 2006

Arteriosclerosis, Thrombosis, and Vascular Biology. 2006
Published online before print February 16, 2006, doi: 10.1161/01.ATV.0000210016.89991.2a
A more recent version of this article appeared on May 1, 2006
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Submitted on August 1, 2005
Accepted on February 1, 2006

Optical Imaging of Hydroxyapatite in the Calcified Vasculature of Transgenic Animals

Atif Zaheer ; Monzur Murshed ; Alec M. De Grand ; Timothy G. Morgan ; Gerard Karsenty ; and John V. Frangioni *

From the Department of Radiology (A.Z., A.M.D., J.V.F.) and Division of Hematology/Oncology (J.V.F.), Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Mass; Department of Molecular and Human Genetics (M.M.), Baylor College of Medicine, Houston, Tex; GE Healthcare Biosciences (T.G.M.), Boston, Mass.

* To whom correspondence should be addressed. E-mail: jfrangio{at}bidmc.harvard.edu.

Objective--To detect the hydroxyapatite component of vascular calcification in vivo so that the process of calcium deposition can be studied in transgenic model systems.

Methods and Results--We have previously developed a near-infrared fluorescent bisphosphonate derivative that binds with high affinity and specificity to hydroxyapatite, and an intraoperative near-infrared fluorescence imaging system for small animals. Using these tools, and a transgenic mouse strain with homozygous deletion of the matrix GLA protein (mgp-/-), we demonstrate that the hydroxyapatite component of vascular calcification can be detected in vivo with high sensitivity, specificity, and resolution.

Conclusions--The hydroxyapatite component of vascular calcification can be detected optically, in real-time, without sacrifice of the animal. It is now possible to study the earliest events associated with vascular mineralization, at the cell and organ level, and to monitor the process in living animals.
Key words: bisphosphonates • hydroxyapatite • matrix GLA protein • near-infrared fluorescence imaging • vascular calcification




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