Research Article Open Access Madhumathi et al., Bioceram Dev Appl 2014, 4:1 DOI: 10.4172/2090-5025.1000079 Volume 4 • Issue 1 • 1000079 Bioceram Dev Appl ISSN: 2090-5025 BDA, an open access journal Silver and Gadolinium Ions Co-substituted Hydroxyapatite Nanoparticles as Bimodal Contrast Agent for Medical Imaging Madhumathi K 1 , Sampath Kumar TS 1* , Mohammed Sanjeed T 2 , Sabik Muhammed A 2 , Sahal Nazrudeen 2 and Sharanya D 3 1 Medical Materials Laboratory, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai 600042, India 2 Department of Biomedical Engineering, SMK Fomra Institute of Technology, Kelambakkam, Chennai 603103, India 3 Department of Biomedical Engineering, Sri Ramakrishna Engineering College, Vattamalaipalayam, N.G.G.O colony post, Coimbatore 641022, India *Corresponding author: Sampath Kumar TS, Medical Materials Laboratory, Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai 600042, India, Tel: +91 4422574772; E-mail: tssk@iitm.ac.in Received October 08, 2014; Accepted October 24, 2014; Published October 31, 2014 Citation: Madhumathi K, Kumar STS, Sanjeed MT, Muhammed SA, Nazrudeen S, et al. (2014) Silver and Gadolinium Ions Co-substituted Hydroxyapatite Nanoparticles as Bimodal Contrast Agent for Medical Imaging. Bioceram Dev Appl 4: 079. doi: 10.4172/2090-5025.1000079 Copyright: © 2014 Madhumathi K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Developing multimodal contrast agents is an upcoming area and hydroxyapatite nanoparticles substituted with various elements like gadolinium, eurobium etc., seems to be a promising contrast agent, especially for multimodal imaging of bone-tissue interface. A bimodal contrast agent using silver (Ag + ) and gadolinium (Gd 3+ ) ions co-substituted hydroxyapatite nanoparticles has been developed for X-ray and magnetic resonance imaging. Ag + and Gd 3+ ions were co-substituted into hydroxyapatite at various atomic percentages (Ag:Gd=0.25:0.25, 0.25:0.5, 0.25:0.75) using microwave accelerated wet chemical synthesis. Pure as well as Ag + and Gd 3+ ions substituted hydroxyapatite samples were also synthesized for comparison. All samples were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy etc., and found to be monophasic, nanocrystalline with the substituted ions. These co-substituted hydroxyapatite samples were then tested in different diagnostic modalities such as X-ray, computed tomography imaging and magnetic resonance imaging. Appreciable variation in contrast was observed with different amount of substitutions. All the Ag + and Gd 3+ ions co-substituted hydroxyapatite nanoparticles showed higher contrast in all imaging modalities compared to those substituted with either Ag + or Gd 3+ ions only. Hydroxyapatite sample co-substituted with 0.25Ag and 0.75Gd at. % substitution showed the best bimodal CT-MRI contrast. Keywords: Hydroxyapatite; Bimodal imaging; CT-MRI contrast; Silver-gadolinium substitution; Nanoparticles Introduction Currently, various non-invasive imaging modalities such as com- puted X-ray tomography (CT), magnetic resonance imaging (MRI), ultrasound imaging (USI), positron emission tomography (PET) and single photon emission spectroscopy (SPECT) are used in the diagnosis of various diseases [1,2]. Each imaging modality has its own applica- tions, merits and demerits. Since, a single imaging technique does not give a complete perspective on all aspects of a disease/disorder, it is common in clinical practice to rely on two or more techniques to ar- rive at an accurate and reliable diagnosis. For example, combinations of CT/MRI, PET/SPECT etc., are used for radiation treatment plan- ning and cancer diagnosis respectively [1,2]. Hence, multimodal imag- ing is a rapidly advancing field given its clinical importance with im- proved patient safety and lowered cost. Multimodal imaging implicates combining several imaging techniques by developing multifunctional contrast agents. Until now, only separate contrast agents are used for each imaging mode like iodine or barium compounds as radio con- trast agents for X-ray/CT imaging, paramagnetic Gd 3+ compounds and super paramagnetic iron oxide (SPIO) nanoparticles for MR imaging [3]. Studies are being carried out to combine different modes of imag- ing by developing a single contrast agent based on polymers, liposomes and inorganic nanoparticles like hydroxyapatite (HA) [3,4]. Some of the ideal properties required for a contrast agent include colloidal stability independent of pH and temperature variations, high selectivity and sensi- tivity, sufficient blood circulation time and easy renal clearance [5,6]. Mul- timodal contrast agents based on inorganic nanoparticles have attracted considerable attention due to their small tunable size and attractive physi- cal and chemical properties including bio-functionalization, prolonged circulating half-life, passive accumulation at tumor site through enhanced permeation and retention (EPR) effect [5]. e nanoparticulate contrast agents have been reported to provide enhanced signal sensitivity and im- part information at the cellular levels [7]. Bioceramics like hydroxyapatite (HA, mineral component of bone) which has been extensively studied as a bone substitute or drug delivery carrier has also shown potential as a contrast agent when substituted with various ions like Gd 3+ , Eu 3+ , Tb 3+ etc., for MRI and fluorescent imaging [8-10]. HA nanoparticles are non-toxic and provide flexibility in terms of ion substitutions in the crystal structure. ey also contain multiple functional groups enabling targeted imaging and provide the ragnostic value by serving as drug carriers as well [11,12]. ese properties make nano HA as an attractive multimodal contrast agent. Among all the imaging techniques, CT and MRI are widely used clinically and thus developing a single CT-MRI contrast agent may enhance the imaging capabilities especially at the bone-tissue interface. MRI is a non-ionizing imaging method that offers a high soſt tissue contrast and provides high spatial resolution. is technique is based on measuring water proton relaxation states under a magnetic field [5,13]. Gadolinium (III) or Gd 3+ ion is a commonly used positive contrast for MRI by enhancing the T1 relaxation in T1 weighed images. Gd 3+ ion has been incorporated into silica, carbon nanotubes etc., to provide brighter MR signal [14,15]. CT is the most powerful imaging technique employing X-ray ionization and found to be very ideal for hard tissue imaging [5]. Iodinated nanoparticles, gold nanoparticles, iron oxide nanoparticles etc., are popular nanoparticulate contrast agents studied for CT/X-ray imaging [5]. In our study, we have co- Bioceramics Development and Applications B i o c e r a m i c s D e v e lo p m e n t a n d A p p l i c a t i o n s ISSN: 2090-5025