title: Multifunctional calcium phosphate nano-contrast agent for combined nuclear, magnetic and near-infrared in vivo imaging.
abstract: 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 (Gd(3+)), and labeled with 99m-Technetium-methylene diphosphonate ((99m)Tc-MDP) for combined optical, magnetic and nuclear imaging. In order to obtain the desired tri-modal contrast properties, the concentrations of ICG, Gd(3+) and (99m)Tc 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. In vivo 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 in vivo.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Cochin 682041, Kerala, India.
authors.forename: Anusha
authors.initials: A
authors.lastname: Ashokan
authors.forename: Genekehal S
authors.initials: GS
authors.lastname: Gowd
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Somasundaram
authors.forename: Arun
authors.initials: A
authors.lastname: Bhupathi
authors.forename: Reshmi
authors.initials: R
authors.lastname: Peethambaran
authors.forename: A K K
authors.initials: AK
authors.lastname: Unni
authors.forename: Shanmugasundaram
authors.initials: S
authors.lastname: Palaniswamy
authors.forename: Shantikumar V
authors.initials: SV
authors.lastname: Nair
authors.forename: Manzoor
authors.initials: M
authors.lastname: Koyakutty
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000032:analysis* / Q000633:toxicity; D003287:Contrast Media / Q000032:analysis* / Q000633:toxicity; D003952:Diagnostic Imaging / Q000379:methods; D005682:Gadolinium / Q000032:analysis / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green / Q000032:analysis / Q000633:toxicity; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D053758:Nanoparticles / Q000032:analysis* / Q000633:toxicity / Q000648:ultrastructure; D061848:Optical Imaging / Q000379:methods*; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013669:Technetium Tc 99m Medronate / Q000032:analysis / Q000633:toxicity; D014965:X-Rays
chemical_list: D002130:Calcium Phosphates; D003287:Contrast Media; C020243:calcium phosphate; D005682:Gadolinium; D007208:Indocyanine Green; D013669:Technetium Tc 99m Medronate