Dendrimer Nanocomposites as Multifunctional X-ray Contrast Agents
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1064-PP06-18
Dendrimer Nanocomposites as Multifunctional X-ray Contrast Agents Teyeb Ould Ely1, Manju Sharma1, Wojciech Lesniak1, Donald L. Klippenstein2, Barbara A. Foster3, and Lajos P. Balogh1 1 Radiation Medicine, RoswellPark Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263 2 Radiology, RoswellPark Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263 3 Pharmacology & Therapeutics, RoswellPark Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263 ABSTRACT We synthesized dendrimer composite nanoparticles and investigated their potential for traditional X-ray imaging and Computed Tomography (CT). These new X-ray contrast agents show better contrast compared to traditional iodine-based contrast agents, and are expected to clear from the blood much slower than commercial agents, permitting longer imaging times. We have also investigated their safety profile in terms of viscosity and osmotic pressure. INTRODUCTION The market of X-ray contrast agents remains dominated by contrast agents composed of mostly iodinated ionic or nonionic small molecules that distribute primarily in the extracellular space [1-4]. There is intense interest in synthesizing new contrast agents and in evaluating their safety profiles. The amount of contrast enhancement obtained in individual patients depends on the contrast agent characteristics, such as X-ray absorption, concentration, and the parameters of the contrast injection protocol, such as flux and dose. Meanwhile, contrast agent characteristics such as osmolality and viscosity play an important role in the safety profile of an agent.[1, 4] The need of new functional contrast agents is specifically urgent for angiographic imaging purposes (high contrast in the cardio-vascular system) since it is only possible on a time scale which is limited to minutes or sometimes even seconds. If the peak time of the contrast agent concentration in the blood is missed, a second inconvenient and potentially hazardous injection of a high volume (up to 200 ml, 300 mgI/ml)[1] of contrast material into the patient is necessary. Therefore, the development of X-ray contrast agents which would provide higher Xray absorption with minimal dose and longer imaging times is highly desired [2]. So far, there have been few reports on macromolecular, water-soluble iodinated agents, all of which are based upon linear synthetic polymers or functionalized starches [3, 5-10]. The structure and size of these carriers are presently being optimized, but so far no compound has reached the status of clinical applications [11]. Possible limitations to overcome are synthetic problems such as drug uniformity, reproducible production of pure compounds and analytical issues, such as adequate characterization and safety profile. The encapsulation of high atomic number elements in iodine modified dendrimers has not yet been reported to our knowledge. This combination is very promising since the inorganic
components of these hybrid systems present strong X-ray absorption that could be maximized by tun
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