Future Challenges for Further Advancement

Future advancement in biomedical imaging will likely involve a more specific approach for targeting nanoparticles to the molecules of interest. The challenge here is to minimize non- specific uptake (i.e., uptake by macrophages and other cells of the reticulo-endothelial system), unless, of course, the goal is to visualize the presence or absence of macrophage-type cells in certain disease processes. Particles should be sufficiently small to penetrate endothelial barriers, but should have long- circulating blood half lives in order to facilitate an accumulation at the target. This could be achieved by a manipulation of the surface charge or an

Figure 1.1. Quantum dot particles come in a variety of fluorescent colors depending on the size of the semiconductor crystal. The color is determined by the size of the particle and is thus tunable by synthesis. The size of the quantum dot dictates the band gap, with the band gap being the energy required to lift an electron from its valence band, filled with electrons, to its conduction band, which is empty. When an electron falls from the conduction band back down to the valence band, eliminating a hole, the lost energy is emitted as light whose color then corresponds to the band gap. The quantum dot in (A) is composed of GaAs and those in (B) are composed of CdSe and CdTe. In (A), green represents the total electron charge density for a quantum dot of 465 atoms. Image (A) is taken from http://www.lbl.gov/Science-Articles/Archive/Quantum-Dot-Electronics.html and image (B) from http://www.rsc.org/chemistryworld/News/2005/ September/19090501.asp.

Figure 1.1. Quantum dot particles come in a variety of fluorescent colors depending on the size of the semiconductor crystal. The color is determined by the size of the particle and is thus tunable by synthesis. The size of the quantum dot dictates the band gap, with the band gap being the energy required to lift an electron from its valence band, filled with electrons, to its conduction band, which is empty. When an electron falls from the conduction band back down to the valence band, eliminating a hole, the lost energy is emitted as light whose color then corresponds to the band gap. The quantum dot in (A) is composed of GaAs and those in (B) are composed of CdSe and CdTe. In (A), green represents the total electron charge density for a quantum dot of 465 atoms. Image (A) is taken from http://www.lbl.gov/Science-Articles/Archive/Quantum-Dot-Electronics.html and image (B) from http://www.rsc.org/chemistryworld/News/2005/ September/19090501.asp.

incorporation of stealth coatings. Yet, nanoparticles should be large enough to enable amplification of signal changes upon target binding.

Ideally, nanoparticle formulations should be stable for prolonged times and composed of materials that are biocompatible or biodegradable, unless the concentrations are so low that the tracer principle applies. A relatively new area is the use of diagnostic "smart" agents that can act as sensors for probing the enzyme/protein environment. These beacons may shed more light on how certain tumor processes take place. New types of diagnostic nanoparticles are constantly being developed. Some involve new agents for older imaging techniques (e.g., radiopaque bismuth particles for CT imaging) (Rabin et al., 2006), and older formulations for new imaging techniques (e.g., liposomes for CEST MR imaging) (Aime et al., 2005). With more variations and integrations of imaging techniques on the horizon, the future of nanoparticles as an imaging platform is bright and mighty. The following chapters each cover current applications of nanopar-ticle imaging agents, which may pave the way toward further refinements and innovations in biomedical imaging.

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Part 1

(Para)magnetic Nanoparticles: Applications in Magnetic Resonance Imaging

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