Publication Type:

Journal Article


Biomaterials, Volume 34, Number 29, p.7143-7157 (2013)



animal experiment, animal tissue, Animals, article, Calcium phosphate, calcium phosphate nanoparticle, Calcium phosphate nanoparticles, Calcium Phosphates, Contrast Media, contrast medium, controlled study, Diagnosis, diagnostic imaging, fluorescence imaging, gadolinium, Hemolysis, Histology, Humans, in vivo study, In-Vivo imaging, indocyanine green, Infrared devices, Infrared imaging, Magnetic contrast, Magnetic Resonance Imaging, medronic acid, Mice, mononuclear cell, mouse, Mus, nanocontrast agent, Nanomagnetics, nanoparticle, Nanoparticles, near infrared spectroscopy, Near-Infrared, NIR contrast, nonhuman, Nuclear contrast, nuclear magnetic resonance imaging, Optical imaging, polyethyleneimine, priority journal, Spectroscopy, technetium 99m, Technetium Tc 99m Medronate, unclassified drug, X-Rays


Combination of three imaging techniques such as nuclear, magnetic and near-infrared fluorescence can aid in improved diagnosis of disease by synergizing specific advantages of each of these techniques such as deep tissue penetration of radiation signals, anatomical and functional details provided by magnetic contrast and better spatial resolution of optical signals. In the present work, we report the development of a multimodal contrast agent based on calcium phosphate nanoparticles (nCP), doped with both indocyanine green (ICG) and Gadolinium (Gd3+), and labeled with 99m-Technetium-methylene diphosphonate (99mTc-MDP) for combined optical, magnetic and nuclear imaging. In order to obtain the desired tri-modal contrast properties, the concentrations of ICG, Gd3+ and 99mTc were optimized at  0.15wt%, 3.38at% and  0.002ng/mg of nCP, respectively. The leaching-out of ICG was protected by an additional coating of polyethyleneimine (PEI). Toxicological evaluation of the final construct carried out on healthy human mononuclear cells, red-blood cells and platelets, showed excellent hemocompatibility. Invivo multimodal imaging using mice models revealed the ability to provide near-infrared, magnetic and nuclear contrast simultaneously. The nanoparticles also showed the potential for improved MR based angio-imaging of liver. Retention of intravenously administrated nanoparticles in the liver was reduced with PEGylation and the clearance was observed within 48h without causing any major histological changes in vital organs. Thus, we developed a non-toxic tri-modal nano-contrast agent using calcium phosphate nanoparticles and demonstrated its potential for combined nuclear, magnetic and near-infrared imaging invivo. © 2013 Elsevier Ltd.


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Cite this Research Publication

, “Multifunctional calcium phosphate nano-contrast agent for combined nuclear, magnetic and near-infrared invivo imaging”, Biomaterials, vol. 34, pp. 7143-7157, 2013.