Narrow Results

This paper delves into the history of MARS photon-counting CT and its technology origins in particle physics at the European Organization for Nuclear Research (CERN). The story begins at CERN, a world-class facility for research into fundamental physics. In the 1960s, charged particle experiments at CERN involved the slow and labor-intensive work of examining millions of photographs from bubble or spark chambers. In the 1970s, semiconductor detector technology changed nuclear and particle physics, and the world at large. As its name implies, semiconductor material conducts current, but this current can be modified, especially by a quantum of light or other radiation. During the development of semiconductor detector technology, the potential benefit of detecting X-ray photons became evident, leading to the development of the Medipix family of imaging devices in the 1990s. In the early 2000s, researchers from New Zealand took the Medipix detector and began to research and develop spectral molecular imaging for the clinic. Their work produced the MARS photon-counting CT, which promises to significantly advance current CT, develop a new standard of care, and improve health outcomes for millions of patients world-wide. Taking MARS to the clinic will be discussed, including investigation of potential clinical applications and the future direction of MARS technology.

Nanomedicine is to apply and further develop nanotechnology to solve problems in medicine, i.e. to diagnose, treat and prevent diseases at the cellular and molecular level. This article demonstrates through a full spectrum of proof-of-concept research, from nanoparticle preparation and characterization, in vitro drug release and cytotoxicity, to in vivo pharmacokinetics and xenograft model, how nanoparticles of biodegradable polymers could provide an ideal solution for the problems encountered in the current regimen of chemotherapy. A system of vitamin E TPGS coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles is used as an example for paclitaxel formulation as a model drug. In vitro HT-29 cancer cell viability experiment demonstrated that the paclitaxel formulated in the nanoparticles could be 5.64 times more effective than Taxol^® after 24 hr of treatment. In vivo pharmacokinetics showed that the drug formulated in the nanoparticles could achieve 3.9 times higher therapeutic effects judged by area-under-the curve (AUC). One shot can realize sustainable chemotherapy of 168 hr compared with 22 hr for Taxol^® at a single 10 mg/kg dose. Xenograft tumor model further confirmed the advantages of the nanoparticle formulation versus Taxol^®.

Technetium and Rhenium are the two lower elements in the manganese triad. Whereas rhenium is known as an important part of high resistance alloys, technetium is mostly known as a cumbersome product of nuclear fission. It is less known that its metastable isotope ^99mTc is of utmost importance in nuclear medicine diagnosis. The technical application of elemental rhenium is currently complemented by investigations of its isotope ¹⁸⁸Re, which could play a central role in the future for internal, targeted radiotherapy. This article will briefly describe the basic principles behind diagnostic methods with radionuclides for molecular imaging, review the ^99mTc-based radiopharmaceuticals currently in clinical routine and focus on the chemical challenges and current developments towards improved, radiolabeled compounds for diagnosis and therapy in nuclear medicine.

This review article briefly describes the available synthetic approaches for meso-arylporphyrins giving particular emphasis for one-pot nitrobenzene and nitrobenzene/NaY methods regarding the synthesis of meso-halogenated arylporphyrins. The review also describes the relevant applications of these halogenated porphyrins and their metalloporphyrin counterparts, prepared via nitrobenzene method, as photosensitizers for therapy (PDT and PDI), diagnostic (molecular contrast agents) and also for catalytic oxidation and CO₂ cycloaddition reactions to epoxides.

Photoacoustic molecular imaging, combined with the reporter-gene technique, can provide a valuable tool for cancer research. The expression of the lacZ reporter gene can be imaged using photoacoustic imaging following the injection of X-gal, a colorimetric assay for the lacZ-encoded enzyme β-galactosidase. Dual-wavelength photoacoustic microscopy was used to non-invasively image the detailed morphology of a lacZ-marked 9L gliosarcoma and its surrounding microvasculature simultaneously in vivo, with a superior resolution on the order of 10 μm. Tumor-feeding vessels were found, and the expression level of lacZ in tumor was estimated. With future development of new absorption-enhancing reporter-gene systems, we anticipate this strategy can lead to a better understanding of the role of tumor metabolism in cancer initiation, progression, and metastasis, and in its response to therapy.

In this study, we report the fabrication of engineered iron oxide magnetic nanoparticles (MNPs) functionalized with anti-human epidermal growth factor receptor type 2 (HER2) antibody to target the tumor antigen HER2. The Fc-directed conjugation of antibodies to the MNPs aids their efficient immunospecific targeting through free Fab portions. The directional specificity of conjugation was verified on a macrophage cell line. Immunofluorescence studies on macrophages treated with functionalized MNPs and free anti-HER2 antibody revealed that the antibody molecules bind to the MNPs predominantly through their Fc portion. Different cell lines with different HER2 expression levels were used to test the specificity of our functionalized nanoprobe for molecular targeting applications. The results of cell line targeting demonstrate that these engineered MNPs are able to differentiate between cell lines with different levels of HER2 expression.

There is a growing realization that cell-to-cell variations in gene expression have important biological consequences underlying phenotype diversity and cell fate. Although analytical tools for measuring gene expression, such as DNA microarrays, reverse-transcriptase PCR and in situ hybridization have been widely utilized to discover the role of genetic variations in governing cellular behavior, these methods are performed in cell lysates and/or on fixed cells, and therefore lack the ability to provide comprehensive spatial-dynamic information on gene expression. This has invoked the recent development of molecular imaging strategies capable of illuminating the distribution and dynamics of RNA molecules in living cells. In this review, we describe a class of molecular imaging probes known as molecular beacons (MBs), which have increasingly become the probe of choice for imaging RNA in living cells. In addition, we present the major challenges that can limit the ability of MBs to provide accurate measurements of RNA, and discuss efforts that have been made to overcome these challenges. It is envisioned that with continued refinement of the MB design, MBs will eventually become an indispensable tool for analyzing gene expression in biology and medicine.

Near-infrared fluorescence (NIRF) imaging involves the separation of weak fluorescence signals from backscattered excitation light. The measurement sensitivity of current NIRF imaging systems is limited by the excitation light leakage through rejection filters. In this contribution, the authors demonstrate that the excitation light leakage can be suppressed upon using appropriate filter combination and permutations. The excitation light leakage and measurement sensitivity were assessed and compared in this study by computing the transmission ratios of excitation to emission light collected and the signal-to-noise ratios in well-controlled phantom studies with different filter combinations and permutations. Using appropriate filter combinations and permutations, we observe as much as two orders of magnitude reduction in the transmission ratio and higher signal-to-noise ratio.

Photoacoustic imaging (PAI) breaks through the optical diffusion limit by making use of the PA effect. By converting incident photons into ultrasonic waves, PAI combines high contrast of optical imaging and high spatial resolution in depth tissue of ultrasound imaging in a single imaging modality. This imaging modality has now shown potential for molecular imaging, which enables visualization of biological processes with systemically introduced functional nanoparticles. In the current review, the potentials of different optical nanoprobes as PAI contrast agents were elucidated and discussed.

Molecular imaging is an important technology to clarify biological and medical uncertainties in the 21th century. This is best realized via in vivo imaging of biological processes in small animals. Thus, a special high resolution imager dedicated for small animals is required. We recently installed a high resolution animal positron emission tomography (PET) scanner (microPET R4) for doing in vivo molecular imaging of gene expression. This paper describes the performance evaluation of our microPET R4 scanner. The microPET R4 scanner is a dedicated PET for studies of rodents. The system is composed of 96 detector modules, each with an 8 × 8 array of 2.1 × 2.1 × 10 mm³ lutetium oxyorthosilicate (LSO) crystals, arranged as 32 crystal rings and 14.8 cm in diameter. The detector crystals are coupled to a Hamamatsu R5900-C8 position sensitive photomultiplier tube (PS-PMT) via a 10 cm long optical fiber bundle. The system operates in 3D mode without inter-plane septa, acquiring data in list mode. A number of scanner parameters such as sensitivity, spatial resolution and energy resolution were determined in this work. In the center of field of view (FOV) a maximal sensitivity of 21.04 cps/kBq was calculated from a measurement with a germanium-68 point source with an energy window of 250-750 keV. Spatial resolution of 2.03 mm (FORB+2D-FBPJ/1.61 mm (FORB + 2D-OSEM) full width at half maximum (FWHM) in the tangential direction and 2.07 mm (2D-FBP)/1.65 mm (2D-OSEM) FWHM in the radial direction were measured in the center with a 0.28 mm diameter ¹⁸F-FDG line source. The energy resolution of the scanner was measured across all crystals ranging from 13.9% to around 34.6% with a mean of 18.45%. The results show that the microPET R4 is a suitable PET scanner for imaging small animals like mice and rats.

Objectives: We have developed a portable system compatible with various clinical gamma cameras to perform three-dimensional (3D) small-animal molecular imaging. The spatial resolution of this system is close to that of commercial animal imaging systems, although its cost is much lower. Methods: The portable system consists of a rotating stage, a leveling plate, a line source phantom, and a calibration phantom. To obtain high-resolution single-photon emission computed tomography (SPECT) images, we developed several methods for system alignment and applied geometric calibration. The projections of the subject were reimaged according to the calibration parameters and reconstructed by the 3D ordered subsets expectation maximization (OS-EM) algorithm. Results: The resulting images of the microdeluxe phantom showed 2.4-mm cold rods. The image quality of phantom scanning was stable when the portable system was applied to various gamma cameras from different manufacturers. The resultant images of a ^99mTc-MDP bone scan of a mouse showed details of the spine, femur, pelvis, and tail. Furthermore, a radiopharmaceutical study of ^99mTc-HYNIC-Annexin V on a liver inflammation-induced mouse was carried out to demonstrate the feasibility of this system for small-animal molecular imaging. Conclusions: The newly developed portable system was compatible with various gamma cameras and enabled successful performance of small-animal molecular imaging.

The real-time tracking of a single molecule is a very useful technique to demonstrate the dynamics of drugs in vivo. We have succeeded in capturing the specific delivery of trastuzumab conjugated with a Quantum dot and fluorescent substances of various sizes in animal models. These results revealed the particular movements of drugs or particles in the tumor tissues. Knowledge of the detailed movement of particles incorporated in drugs can lead to improvement of the design of drugs. We are applying this single molecular imaging technique to estimate the efficacy of a drug delivery system.

Nanomedicine is the application of nanotechnology to prevention, diagnosis and treatment of human disease. It has a potential to change medical science dramatically in the 21 st century. However, the research field is in its infancy, and it is necessary to grasp mechanism of pharmacokinetics, the toxicity on the occasion of application to medical treatment, in particular on the aspect of safety of the materials and devices. Here, we describe fluorescent nono-particles for sentinel node navigation for breast cancer surgery in experimental model, which have shown the potential to be an alternative to existing tracers in the detection of the sentinel node of if we select the appropriate particle size and wavelength. We also describe generation of CdSe nanoparticles, Quantum Dots (QDs) conjugated with monoclonal anti-HER2 antibody, Trastuzumab, for molecular imaging of breast cancer cells. The QDs-Trastuzumab complex coated with PEG was successfully made without decreasing the titer of antibody. We established a high resolution of 3D in vivo microscopic system as a novel imaging method at molecular level. The cancer cells expressing HER2 protein were visualized by the nanoparticles in vivo at subcellular resolution, suggesting future utilization of the system in medical applications including drug delivery system to target the primary and metastatic tumors. Future innovation in cancer imaging, not only at cellular level but also at molecular level, by synthesizing diagnostic agents with nanoparticles, is now expected.

Semiconductor quantum dots (Qdot) are nanometer-sized crystals which improved brightness, resistance against photobleaching compared with organic dyes and fluorescent proteins. Therefore, Qdot are thought to become new adjuncts of fluorescent bioprobes for medical applications, especially for cancer imaging. We have used Qdot conjugated with monoclonal anti-HER2 antibody (Trastuzumab) for molecular imaging of breast cancer cells. We utilized poly ethylene glycol (PEG) coated Qdot-Trastuzumab complex to label a cell membrane of HER2 overexpressing breast cancer cells. Using this complex, we established the in vivo fluorescent cancer imaging method. After injection of the Qdot-Trastuzumab complex to the human breast cancer xenograft mouse model, the accumulation of Qdot to the tumor tissue was clearly observed at subcellular resolution with the original 3D intravital microscopic system. This suggests that we can eventually develop a novel cancer imaging and drug tracking system.

This review article briefly describes the available synthetic approaches for mesoarylporphyrins giving particular emphasis for one-pot nitrobenzene and nitrobenzene/NaY methods regarding the synthesis of meso-halogenated arylporphyrins. The review also describes the relevant applications of these halogenated porphyrins and their metalloporphyrin counterparts, prepared via nitrobenzene method, as photosensitizers for therapy (PDT and PDI), diagnostic (molecular contrast agents) and also for catalytic oxidation and CO₂ cycloaddition reactions to epoxides.

Molecular imaging is a relatively new field in which a variety of imaging modalities are used to evaluate cellular and molecular process in vivo. From within this multidisciplinary field, this chapter focuses on the methodology of positron emission tomography (PET) imaging of small animals. While clinical nuclear medicine imaging of the musculoskeletal system primarily encompasses MDP bone scans and FDG PET scans for the evaluation of osseous malignancy, the tracer of choice for research applications in small animals (usually mice or rats) is fluorine-18–fluoride ion (F⁻). This tracer is incorporated into the hydroxyapatite matrix, and is therefore a preferential bone-imaging agent. It is otherwise nonspecific and has been used for a variety of applications including imaging fractures, microdamages, and bone cancers. After detailing the materials and methods necessary to perform PET imaging of small animals using F⁻, a review of the current literature in this area is provided with comprehensive examples of the types of images that can be obtained for both visual and quantitative representations of various musculoskeletal processes. Pitfalls for this type of imaging are also discussed. Future applications of this powerful modality are expected to grow as the technology improves.

Nanomedicine is to apply and further develop nanotechnology to solve problems in medicine, i.e. to diagnose, treat and prevent diseases at the cellular and molecular level. This article demonstrates through a full spectrum of proof-of-concept research, from nanoparticle preparation and characterization, in vitro drug release and cytotoxicity, to in vivo pharmacokinetics and xenograft model, how nanoparticles of biodegradable polymers could provide an ideal solution for the problems encountered in the current regimen of chemotherapy. A system of vitamin E TPGS coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles is used as an example for paclitaxel formulation as a model drug. In vitro HT-29 cancer cell viability experiment demonstrated that the paclitaxel formulated in the nanoparticles could be 5.64 times more effective than Taxol^® after 24 hr of treatment. In vivo pharmacokinetics showed that the drug formulated in the nanoparticles could achieve 3.9 times higher therapeutic effects judged by area-under-the curve (AUC). One shot can realize sustainable chemotherapy of 168 hr compared with 22 hr for Taxol^® at a single 10mg/kg dose. Xenograft tumor model further confirmed the advantages of the nanoparticle formulation versus Taxol^®.

Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, http://www.ncbi.nlm.nih.gov/books/NBK5330/), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250–300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

Nanomedicine clearly offers unique tools to address intractable medical problems in cancer and cardiovascular disease from entirely new perspectives. Among the theranostic options emerging in this new wave of biotechnology development, the perfluorocarbon nanoparticles have shown robust potential in vivo for diagnosing, characterizing, treating and following proliferating cancers, progressive atherosclerosis, rheumatoid arthritis and much more. These molecular imaging agents have been demonstrated for use with ultrasound, MRI, CT, and SPECT/CT. Moreover, the synergism of imaging for confirmation of therapeutic delivery, for dosimetry, and for noninvasively following early treatment responses is discussed. Image-guided drug delivery based on nanotechnology is emerging as a powerful clinical opportunity, and PFC nanoparticles are among the leading technologies reaching clinical testing today with this potential.