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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1132.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Optical Imaging of Hydroxyapatite in the Calcified Vasculature of Transgenic Animals

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

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

Correspondence to John V. Frangioni, MD, PhD, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Room SL-B05, Boston, MA 02215. 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.

Presently, the hydroxyapatite component of vascular calcification cannot be detected optically. We have developed a near-infrared fluorescent light-based method for imaging hydroxyapatite deposition in the vasculature. It is now possible to study early events associated with vascular mineralization, and to the monitor the process in living animals.

Key Words: bisphosphonates • hydroxyapatite • matrix GLA protein • near-infrared fluorescence imaging • vascular calcification

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