Molecular imaging with surface-enhanced Raman spectroscopy nanoparticle reporters
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Introduction Molecular imaging scans living subjects (rodents, primates, humans) and utilizes electromagnetic (e.g., near infrared light) or acoustic signals to study gene expression or protein levels in deep tissues.1,2 Molecular imaging can measure oncogenesis (tumor growth), angiogenesis (blood vessel growth), and metabolism and is in contrast to traditional imaging modalities that image only anatomy. For example, computed tomography (CT) is a traditional anatomic technique that can image bone, tissue, and tumors, but it does not indicate the biological activity of the tissue. In contrast, positron emission tomography (PET) with 18F-2-fluoro-2-deoxyglucose is a molecular imaging modality that produces a map of glucose metabolism. Molecular imaging experiments typically use injected molecules known as imaging agents or molecular probes. Such an imaging agent translates the biology into an imaging signal; a schematic of such a probe is shown in Figure 1. Here, the probe acts as an interface between the biology under study and the imaging equipment used to collect data and create images. A wide variety of molecular imaging modalities have been reviewed.1 Magnetic resonance imaging (MRI), fluorescence/ bioluminescence, ultrasound, PET, SPECT (single photon emission computed tomography), CT, PET/CT, and PET/MRI have all been employed for molecular imaging. PET and SPECT are perhaps the most evolved molecular imaging modalities and are the workhorses of molecular imaging. However, PET
and most other molecular imaging modalities suffer from one common and significant limitation—the capacity to measure multiple imaging biomarkers concurrently (i.e., multiplexing). As the deep biological complexity of cancer and other diseases is further defined with genomics and proteomics, the ability to measure multiple biomarkers concurrently, in vivo, and with high temporal and spatial resolution will increasingly become a real need. In PET, every imaging agent produces a signal with the same energy. When an emitted positron combines with an electron, it produces two 511 KeV gamma rays. Thus, PET is quantitative but cannot multiplex due to this limitation; it is a “black and white” technique, yielding no spectral data. While optical imaging with fluorophores and luminescent/fluorescent proteins offers more opportunities for multiplexing, these are realistically limited to, at most, 2–3 different color channels because of their broad emission profiles that are limited to the 680–900 nm range, where photons encounter the least resistance from hemoglobin, melanin, water, and other components of tissue. This area of the electromagnetic spectra is known as the “optical window” and is illustrated as the red-shaded box in Figure 2a. While the narrow emission spectra (30–60 nm full width at half maximum) of quantum dots has the potential to improve multiplexing,3 this technology is usually limited by the toxicity concerns of these heavy metal-based probes and their relatively broad emission spectra (Figure 2a).
Jesse V. Jokerst, Molecular Imagin
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