Molecular imaging, first developed to localise antigens in light microscopy, now encompasses all imaging modalities including those used in clinical care: optical imaging, nuclear medical imaging, ultrasound imaging, CT, MRI, and photoacoustic imaging. Molecular imaging always requires accumulation of contrast agent in the target site, often achieved most efficiently by steering nanoparticles containing contrast agent into the target. This entails accessing target molecules hidden behind tissue barriers, necessitating the use of targeting groups. For imaging modalities with low sensitivity, nanoparticles bearing multiple contrast groups provide signal amplification. The same nanoparticles can in principle deliver both contrast medium and drug, allowing monitoring of biodistribution and therapeutic activity simultaneously (theranostics). Nanoparticles with multiple bioadhesive sites for target recognition and binding will be larger than 20 nm diameter. They share functionalities with many subcellular organelles (ribosomes, proteasomes, ion channels, and transport vesicles) and are of similar sizes. The materials used to synthesise nanoparticles include natural proteins and polymers, artificial polymers, dendrimers, fullerenes and other carbon-based structures, lipid-water micelles, viral capsids, metals, metal oxides, and ceramics. Signal generators incorporated into nanoparticles include iron oxide, gadolinium, fluorine, iodine, bismuth, radionuclides, quantum dots, and metal nanoclusters. Diagnostic imaging applications, now appearing, include sentinal node localisation and stem cell tracking.
Packaging small-molecule drugs into nanoparticles improves their bio-availability, bio-compatibility and safety profiles. Multifunctional particles carrying large drug payloads for targeted transport, immune evasion and favourable drug release kinetics at the target site, require a certain minimum size usually 30-300 nm diameter, so are nanoparticles. Targeting particles to a disease site can signal the presence of the disease site, block a function there, or deliver a drug to it. Targeted nanocarriers must navigate through blood-tissue barriers, varying in strength between organs and highest in the brain, to reach target cells. They must enter target cells to contact cytoplasmic targets; specific endocytotic and transcytotic transport mechanisms can be used as trojan horses to ferry nanoparticles across cellular barriers. Specific ligands to cell surface receptors, antibodies and antibody fragments, and aptamers can all access such transport mechanisms to ferry nanoparticles to their targets. The pharmacokinetics and pharmacodynamics of the targeted drug-bearing particle depend critically on particle size, chemistry, surface charge and other parameters. Particle types for targeting include liposomes, polymer and protein nanoparticles, dendrimers, carbon-based nanoparticles e.g. fullerenes, and others. Immunotargeting by use of monoclonal antibodies, chimeric antibodies and humanized antibodies has now reached the stage of clinical application. High-quality targeting groups are emerging: antibody engineering enables generation of human/like antibody (fragments) and facilitates the search for clinically relevant biomarkers; conjugation of nanocarriers to specific ligands and to aptamers enables specific targeting with improved clinical efficacy. Future developments depend on identification of clinically relevant targets and on raising targeting efficiency of the multifunctional nanocarriers.
Intravital lectin perfusion was combined with computer-guided scanning digital microscopy to map the perfused elements of the vasculature in tumor-bearing mice. High-precision composite images (spatial precision 1.3 micron and optical resolution 1.5 micron) were generated to permit exact positioning, reconstruction, analysis, and mapping of entire tumor cross-sections (c. 1 cm in diameter). Collation of these mosaics with nuclear magnetic resonance maps in the same tumor plane identified sites of rapid contrast medium uptake as tumor blood vessels. Digitized imaging after intravital double labeling allowed polychromatic visualization of two different types of mismatched staining. First, simultaneous application of two lectins, each bearing a different fluorochrome, revealed organ-specific differential processing in the microvascular wall. Second, sequential application of two boluses of one lectin, bearing different fluorochromes successively, distinguished between double-labeled microvessels, representing efficiently perfused vascular segments, and single-labeled microvessels, with inefficient or intermittent perfusion. Intravital lectin perfusion images of blood vessels in the vital functional state thus highlighted biologically significant differences in vessel function and served as high-resolution adjuncts to MR imaging.
We demonstrate bio-medical imaging using a Terahertz quantum cascade laser. This new optoelectronic source of coherent Terahertz radiation allows building a compact imaging system with a large dynamic range and high spatial resolution. We obtain images of a rat brain section at 3.4 THz. Distinct regions of brain tissue rich in fat, proteins, and fluid-filled cavities are resolved showing the high contrast of Terahertz radiation for biological tissue. These results suggest that continuous-wave Terahertz imaging with a carefully chosen wavelength can provide valuable data on samples of biological origin; these data appear complementary to those obtained from white-light images.
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