Emerging Targets in Photopharmacology Lerch, Michael M.; Hansen, Mickel J.; van Dam, Gooitzen M. ...
Angewandte Chemie (International ed.),
September 5, 2016, Letnik:
55, Številka:
37
Journal Article
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The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, ...while achieving unprecedented precision in treatment. By using small molecules, photopharmacology provides a viable alternative to optogenetics. We present here a critical overview of the different pharmacological targets in various organs and a survey of organ systems in the human body that can be addressed in a non‐invasive manner. We discuss the prospects for the selective delivery of light to these organs and the specific requirements for light‐activatable drugs. We also aim to illustrate the druggability of medicinal targets with recent findings and emphasize where conceptually new approaches have to be explored to provide photopharmacology with future opportunities to bring “smart” molecular design ultimately to the realm of clinical use.
Spotlight on the patient: The impressive advances made in the field of photopharmacology in recent years are critically reviewed with respect to the “photodruggability” of medicinal targets and prospects for the selective delivery of light to different organs. This Review is meant to provide a stimulus for chemists to enter this exciting field, with fascinating opportunities to bring “smart” molecular design to the realm of clinical use.
When a biological tissue is illuminated with coherent light, an interference pattern will be formed at the detector, the so-called speckle pattern. Laser speckle contrast imaging (LSCI) is a ...technique based on the dynamic change in this backscattered light as a result of interaction with red blood cells. It can be used to visualize perfusion in various tissues and, even though this technique has been extensively described in the literature, the actual clinical implementation lags behind. We provide an overview of LSCI as a tool to image tissue perfusion. We present a brief introduction to the theory, review clinical studies from various medical fields, and discuss current limitations impeding clinical acceptance.
Laser speckle contrast imaging (LSCI) is so sensitive to motion that it can measure the movement of red blood cells. However, this extreme sensitivity to motion is also its pitfall as the clinical ...translation of LSCI is slowed down due to the inability to deal with motion artefacts. In this paper we study the effectiveness of a real-time, multi-spectral motion artefact correction and compensation by subduing an in vitro flow phantom and ex vivo porcine kidney to computer-controlled motion artefacts. On the in vitro flow phantom, the optical flow showed a good correlation with the total movement. This model results in a better signal-to-noise ratios for multiple imaging distances and the overestimation of perfusion was reduced. In the ex vivo kidney model, the perfusion overestimation was also reduced and we were still able to distinguish between ischemia and non-ischemia in the stabilized data whereas this was not possible in the non-stabilized data. This leads to a notably better perfusion estimation that could open the door to a multitude of new clinical applications for LSCI.
Optoacoustic imaging combines the rich contrast of optical methods with the resolution of ultrasound imaging. It can therefore deliver optical visualization of cancer far deeper in tissue than ...optical microscopy and other conventional optical imaging methods. Technological progress and novel contrast media have resulted in optoacoustic imaging being propagated to basic cancer research and in clinical translation projects. We briefly review recent technological advances, showcase the ability to resolve unique cancer biomarkers based on spectral features at different imaging scales, and highlight the imaging performance achieved in preclinical and clinical imaging applications. .
Bacterial infections represent an increasing problem in modern health care, in particular due to ageing populations and accumulating bacterial resistance to antibiotics. Diagnosis is rarely ...straightforward and consequently treatment is often delayed or indefinite. Therefore, novel tools that can be clinically implemented are urgently needed to accurately and swiftly diagnose infections. Especially, the direct imaging of infections is an attractive option. The challenge of specifically imaging bacterial infections in vivo can be met by targeting bacteria with an imaging agent. Here we review the current status of targeted imaging of bacterial infections, and we discuss advantages and disadvantages of the different approaches. Indeed, significant progress has been made in this field and the clinical implementation of targeted imaging of bacterial infections seems highly feasible. This was recently highlighted by the use of so-called smart activatable probes and a fluorescently labelled derivative of the antibiotic vancomycin. A major challenge remains the selection of the best imaging probes, and we therefore present a set of target selection criteria for clinical implementation of targeted bacterial imaging. Altogether, we conclude that the spectrum of potential applications for targeted bacterial imaging is enormous, ranging from fundamental research on infectious diseases to diagnostic and therapeutic applications.
This review discusses recent advances in the targeted imaging of bacterial infections, a rapidly developing field of microbiological research that aims at distinguishing bacterial infections from sterile inflammation in vivo.
During the last decade, the emerging field of molecular fluorescence imaging has led to the development of tumor-specific fluorescent tracers and an increase in early-phase clinical trials without ...having consensus on a standard methodology for evaluating an optical tracer. By combining multiple complementary state-of-the-art clinical optical imaging techniques, we propose a novel analytical framework for the clinical translation and evaluation of tumor-targeted fluorescent tracers for molecular fluorescence imaging which can be used for a range of tumor types and with different optical tracers. Here we report the implementation of this analytical framework and demonstrate the tumor-specific targeting of escalating doses of the near-infrared fluorescent tracer bevacizumab-800CW on a macroscopic and microscopic level. We subsequently demonstrate an 88% increase in the intraoperative detection rate of tumor-involved margins in primary breast cancer patients, indicating the clinical feasibility and support of future studies to evaluate the definitive clinical impact of fluorescence-guided surgery.
Molecular image-guided surgery has the potential for translating the tools of molecular pathology to real-time guidance in surgery. As a whole, there are incredibly positive indicators of growth, ...including the first United States Food and Drug Administration clearance of an enzyme-biosynthetic-activated probe for surgery guidance, and a growing number of companies producing agents and imaging systems. The strengths and opportunities must be continued but are hampered by important weaknesses and threats within the field. A key issue to solve is the inability of macroscopic imaging tools to resolve microscopic biological disease heterogeneity and the limitations in microscopic systems matching surgery workflow. A related issue is that parsing out true molecular-specific uptake from simple-enhanced permeability and retention is hard and requires extensive pathologic analysis or multiple in vivo tests, comparing fluorescence accumulation with standard histopathology and immunohistochemistry. A related concern in the field is the over-reliance on a finite number of chosen preclinical models, leading to early clinical translation when the probe might not be optimized for high intertumor variation or intratumor heterogeneity. The ultimate potential may require multiple probes, as are used in molecular pathology, and a combination with ultrahigh-resolution imaging and image recognition systems, which capture the data at a finer granularity than is possible by the surgeon. Alternatively, one might choose a more generalized approach by developing the tracer based on generic hallmarks of cancer to create a more "one-size-fits-all" concept, similar to metabolic aberrations as exploited in fluorodeoxyglucose - positron emission tomography (FDG-PET) (i.e., Warburg effect) or tumor acidity. Finally, methods to approach the problem of production cost minimization and regulatory approvals in a manner consistent with the potential revenue of the field will be important. In this area, some solid steps have been demonstrated in the use of fluorescent labeling commercial antibodies and separately in microdosing studies with small molecules.
Antibody-based imaging strategies for cancer Warram, Jason M.; de Boer, Esther; Sorace, Anna G. ...
Cancer and metastasis reviews,
09/2014, Letnik:
33, Številka:
2-3
Journal Article
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Although mainly developed for preclinical research and therapeutic use, antibodies have high antigen specificity, which can be used as a courier to selectively deliver a diagnostic probe or ...therapeutic agent to cancer. It is generally accepted that the optimal antigen for imaging will depend on both the expression in the tumor relative to normal tissue and the homogeneity of expression throughout the tumor mass and between patients. For the purpose of diagnostic imaging, novel antibodies can be developed to target antigens for disease detection, or current FDA-approved antibodies can be repurposed with the covalent addition of an imaging probe. Reuse of therapeutic antibodies for diagnostic purposes reduces translational costs since the safety profile of the antibody is well defined and the agent is already available under conditions suitable for human use. In this review, we will explore a wide range of antibodies and imaging modalities that are being translated to the clinic for cancer identification and surgical treatment.
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