ABSTRACT
Noninvasive and minimally invasive biomedical imaging techniques are valuable tools for clinical diagnostics. e eld of medical imaging has been dominated by structural or anatomical imaging provided by x-ray, magnetic resonance, and ultrasound (US) imaging. In recent years, molecular or functional imaging techniques represented by nuclear [single-photon emission computed tomography (SPECT)/positron emission tomography (PET)] imaging, optical molecular imaging, and contrast enhanced variants of x-ray, magnetic resonance imaging (MRI), US, and multiple hybrid imaging methods [e.g., photoacoustic imaging (PAI)] have rapidly advanced, and are in various stages of progress toward widespread clinical translation. Molecular imaging methods are expected to dominate clinical diagnostics in future. Current molecular imaging research is focused toward developing sensitive and highly specic means of visualizing cellular biochemical events for applications in early-stage cancer detection/staging, image-guided chemotherapy, guided stem cell therapies, image-guided gene therapies, and image-guided surgery/thermoablative therapies (Tallury et al. 2008; Hahn et al. 2010). e primary limitations of current medical imaging techniques include poor spatial resolution, low sensitivity, insuf-cient signal penetration, and inability to multiplex either the imaging targets or contrast agents (Jokerst and Gambhir 2011). At the same time, the eld of nanoparticles (NPs) for medical applications has grown by leaps and bound, and it is increasingly obvious that most limitations of biomedical imaging can be alleviated by NP-mediated methods. As a result, NPs have been applied to all imaging areas, and in this chapter, we will concisely review their impact on medical imaging. NPs for biomedical applications range in sizes from 5 to 1000 nm, are bigger than proteins but smaller than typical cells, and thus exhibit
dierent in vivo pharmacokinetics and pharmacodynamics than conventional imaging and therapeutic agents (Jain et al. 2008; Jokerst and Gambhir 2011). NPs are similar in size and share functionalities with subcellular organelles such as ribosomes, proteasomes, and transport vesicles, and this has been exploited to create unique imaging and therapeutic applications (Debbage and Jaschke 2008). Compared to conventional contrast agents, NPs provide improved in vivo detection and enhanced molecular targeting eciencies via long and engineered circulation times, designed size-dependent clearance and trapping pathways [e.g., enhanced permeability and retention (EPR)-based tumor accumulation], and have multimeric binding capacities to target multiple bioevents of interest and integrate multiple signaling agents of varying types in a single vehicle. Diagnosis with NPs in molecular imaging requires the correlation of the imaging signal with a disease phenotype (Jokerst and Gambhir 2011). e location or intensity of NP signals emerging from the site of interest can then indicate the size and state of the disease. e accumulations of contrast agents can be eciently increased by conning the contrast in a nanoscale structure and exploit its favorable biodistribution and clearance proles. e binding of NPs at sites of interest can be further increased by actively targeting to cell surface receptors or molecular phenotypes of the disease under investigation, and here the large surface provided by NPs allows for the engineering of multiple bioadhesive sites for target recognition and binding. For weak contrasts such as uorophores or short-lived contrasts such as PET tracers, NPs allow signal amplication by storing thousands of signaling entities within their structure and make them available at the site of interest. Furthermore, NPs allow ecient combinations of diering and complementary contrasts such as MR-PET, MR-optical, or photoacoustic-optical, thus combining the wide variations in relative resolution-sensitivity properties of these
6.4 Challenges and Future Outlook ..............................................................................................73 References ...............................................................................................................................................73
