ABSTRACT
Molecular imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), computed tomography (CT), ultrasound and optical imaging are widely used clinically to understand and diagnose various diseases. The characteristics of every modality are summarized in Table 5.1. Every imaging modality has its own advantages and disadvantages and no single technique possesses full capabilities to obtain comprehensive and accurate biological information. For example, MRI and CT have the advantages of high spatial resolution, but they are limited by low sensitivity. On the contrary, optical imaging has very high sensitivity but suffers from low tissue penetration depths. Therefore, by integrating different imaging modalities into a single system, multimodal imaging method can offset the limitations of single imaging modalities. PET/CT is one of the multimodal imaging instruments. The first PET/CT scanner, developed in 1998 by Townsend and his colleagues in collaboration with Siemens Medical, was commercially available in 2001 [6, 7]. By 2003, PET/CT instruments were available from all major clinical instrument manufactures such as GE, Philips, CTI, and Siemens. Today, more than 95% of new PET scanners installed are integrated PET/CT scanners. SPECT/CT was introduced commercially in 2004 [8]. PET/MRI instruments, which have brought much hope for improved patient safety and imaging capacity over PET/CT, are also on the horizon [9]. Imaging probes are used to monitor and trace molecular processes. With the advent of multimodal technology, design and development of new functional molecular imaging probes are of great importance. There are two prerequisites for functional molecular imaging probes: first, they have to provide high spatial resolution as well as high sensitivity in imaging; second, target-specific molecular probes have to be available [10]. Many possible combinations of imaging modalities result in different types of imaging contrast agents. Increasing number of works have reported the fabrication of different inorganic multimodal contrast agents. Some examples include iron oxide nanoparticles conjugated with dye molecules [11, 12], iron oxide/quantum dots (QDs) heterodimers [13-16], and paramagnetic ion (Mn2+)-doped QDs [17, 18]. Rare earth ions possess unique optical and magnetic properties due to their 4f electronic configuration. The 4fn electronic
configuration is shielded by an external 5s25p6 subshell, protecting the 4f electronic transitions from external influences. The technological importance of these elements has attracted a lot of interest in magnetic [19] and optical materials [20], as well as biorelated materials [21]. In this chapter, we will first briefly discuss the imaging modality relevant to this chapter. Rare earth based nanomaterials as potential multimodal contrast agents and their applications in these various imaging modalities will be reviewed. Table 5.1 Characteristics of every modality Modality Resolution Depth Cost Time Imaging agentsPET 1-2 mm No limit High Minutes Radioisotope (18F, 64Cu, 99mTc, 124I)SPECT 1-2 mm No limit High Minutes Radioisotope (18F, 124I, 64Cu, 99mTc)MRI 10-100 μm No limit High Minutes-Hours Paramagnetic ions (Gd3+, Mn2+);Paramagnetic nanoparticles;Superparamagnetic nanoparticles ( iron oxide)Optical 1 μm < 400 μm Low Seconds-Minutes Organic dyes;Fluorescent protein;Rare earth chelate;
QDs;Rare earth nanomaterials;Carbon nanotube;CT 50 μm No limit Medium Minutes Iodine;Gadolinium;Gold nanoparticles; Bismuth sulfide nanoplate;Ultra-sound 50 μm Milli-meters Medium Minutes Microbubble;Perfluorocarbon nanoparticles;
5.1.1 Positron Emission Tomography and Single Photon Emission Computed TomographyPET and SPECT are part of nuclear imaging techniques. They have the advantages of high intrinsic sensitivity and unlimited penetration depth [23]. PET has the additional advantages of being fully
quantitative, providing higher spatial resolution than SPECT [24, 25]. Hundreds of radiotracers based on a wide variety of radionuclides due to β-or γ-rays have been developed and tested in animal and clinical studies. Some examples of the radionuclides are summarized in Table 5.2 [26-28]. The half-lives of these radiotracers are short; thus they need to be produced on site, which increases the cost of imaging. For clinical use, these radiotracers are injected into a patient’s bloodstream. The amount of the radiotracers injected is so small (ng or μg) that the toxicity is usually not a major issue. In PET, the tracers are incorporated into a biologically active molecule, such as fluorodeoxyglucose (FDG). The isotope accumulates in an area of interest in the body, and the radiotracers decay by positron emission. After some time, the distribution of the positron-emitting tracer is calculated by tomographic reconstruction procedures. PET can be used to study neuroreceptors in the brain and other body tissues. Clinical studies include tumors of the brain, breast, lung, lower gastrointestinal tract, study of Alzheimer’s disease, Parkinson’s disease, epilepsy, and coronary artery disease affecting heart muscle metabolism [24, 25, 29].
