There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Suitable labels are at the core of Luminescence and fluorescence imaging and sensing. One of the most exciting, yet also controversial, advances in label technology is the emerging development of quantum dots (QDs)--inorganic nanocrystals with unique optical and chemical properties but complicated surface chemistry--as in vitro and in vivo fluorophores. Here we compare and evaluate the differences in physicochemical properties of common fluorescent labels, focusing on traditional organic dyes and QDs. Our aim is to provide a better understanding of the advantages and limitations of both classes of chromophores, to facilitate label choice and to address future challenges in the rational design and manipulation of QD labels.

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Quantum dots versus organic dyes as fluorescent labels

Core/Shell Nanoparticles: Classes, Properties, Synthesis Mechanisms, Characterization, and Applications

For at least 30 years, matrix metalloproteinases (MMPs) have been heralded as promising targets for cancer therapy on the basis of their massive up-regulation in malignant tissues and their unique ability to degrade all components of the extracellular matrix. Preclinical studies testing the efficacy of MMP suppression in tumor models were so compelling that synthetic metalloproteinase inhibitors (MPIs) were rapidly developed and routed into human clinical trials. The results of these trials have been disappointing. Here we review the studies that brought MPIs into clinical testing and discuss the design and outcome of the trials in light of new information about the cellular source, substrates, and mode of action of MMPs at different stages of tumor progression. The important lessons learned from the MPI experience may be of great value for future studies of MPIs and for cancer drug development in general.

Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations

References http://genesdev.cshlp.org/content/17/5/545.full.html#related-urls Article cited in: http://genesdev.cshlp.org/content/17/5/545.full.html#ref-list-1 This article cites 228 articles, 79 of which can be accessed free at: service Email alerting click here top right corner of the article or Receive free email alerts when new articles cite this article sign up in the box at the Collections Topic (33 articles) Molecular Physiology and Metabolism  (98 articles) Cancer and Disease Models  Articles on similar topics can be found in the following collections

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Molecular imaging in living subjects: seeing fundamental biological processes in a new light

High-resolution in vivo imaging of gene expression is not possible in opaque animals by existing techniques. Here we present a new approach for obtaining such images by magnetic resonance imaging (MRI) using an MRI contrast agent that can indicate reporter gene expression in living animals. We have prepared MRI contrast agents in which the access of water to the first coordination sphere of a chelated paramagnetic ion is blocked with a substrate that can be removed by enzymatic cleavage. Following cleavage, the paramagnetic ion can interact directly with water protons to increase the MR signal. Here, we report an agent where galactopyranose is the blocking group. This group renders the MRI contrast agent sensitive to expression of the commonly used marker gene, β-galactosidase. To cellular resolution, regions of higher intensity in the MR image correlate with regions expressing marker enzyme. These results offer the promise of in vivo mapping of gene expression in transgenic animals and validate a general approach for constructing a family of MRI contrast agents that respond to biological activity.

In vivo visualization of gene expression using magnetic resonance imaging

The conundrum of modality selection in clinical diagnostic imaging is that modalities with the highest sensitivity have relatively poor resolution, while those with high resolution have relatively poor sensitivity In recent years, the idea of using multiple modalities in conjunction has gained in popularity and researchers have come to realize that the complementary abilities of different imaging modalities could be harnessed to great effect by using them in tandem The idea of combining imaging technologies moved to the mainstream with the advent of the first successful commercial fused instruments The first fused PET/CT instrument, developed in 1998 by Townsend and colleagues in collaboration with Siemens Medical, was available commercially in 2001 The “Biograph” was named as one of the “Inventions of the Year” in 2000 by Time magazine, and its success was such that by 2003 fused PET/CT instruments were available from all of the major clinical instrument manufacturers, GE, Philips, CTI, and Siemens1 Over the ensuing years, PET/CT sales increased with such vigor that by the year 2006 there were virtually no sales of standalone PET instruments; all PET sales were as part of multimodality systems2–4 The next wave of innovation has been in PET/MRI-fused instruments, which have generated much hope for improved patient safety and imaging capability over PET/CT Although research on PET/MRI instruments was initiated around the same time as PET/CT, the economic and engineering challenges of merging the two modalities slowed development, and the first commercial PET/MRI prototype for a human scale hybrid scanner was not unveiled until 20075,6 With hybrid technology clearly on the rise, the excitement over these new instruments has triggered a tumult of activity in probe design and development as investigators seek to boost the clinical benefits of hybrid instrument technology

As the preponderance of recent reviews and increase in attention at scientific meetings will attest, there has been a surge in research on multimodal contrast agent development over the past few years5,7–17 For molecular imaging, particularly, the rise in multimodal instrumentation has sparked hopes for new ways to track multiple molecular targets simultaneously, or to use different imaging methods in combination to more clearly delineate localization and expression of biochemical markers In the best of situations, the combined imaging methods and probes work synergistically to allow high-resolution, high-sensitivity investigation of biological activity For example, with dual function probes for PET/MRI, the high sensitivity of PET can be used as a whole body screen to identify regions of interest, thereby reducing the volume of tissue that needs to be scanned; this reduces scan time required for high-resolution imaging by MRI5,18 However, probe design and development has sometimes preceded the identification of clear applications that merit use of the multimodal principle There are many literature examples of probes that are “all dressed up with nowhere to go”; they possess unique physical properties that have yet to find a clear province in medicine or biology Nonetheless, it is not unusual for technology to sometimes presage the need, and it is these advances that can spur imaginative solutions to problems that had been intractable with the previously existing technology The goal of multimodal functionality has already reaped benefits by driving innovation in many areas of chemical synthesis, most notably in nanotechnology

While combining multimodal detectability in the same probe is not necessitated by all applications, there can be advantages to this arrangement A single probe helps to ensure the same pharmacokinetics and colocalization of signal for each modality if that is a concern It also can avoid putting the additional stress on the body’s blood clearance mechanisms that can accompany administration of multiple doses of agents The caveat is that because the sensitivities of different imaging modalities can vary by 3 orders of magnitude, it may not be practical to simply add all functionalities to one molecule, although we will see that is a common design, because the requirements for contrast agent concentrations can be vastly different between modalities In this review, we provide an overview of the many strategies that have been applied to achieve multimodal functionality in a single probe unit These span the range from small molecule to nanoparticulate systems and vary in complexity from facile encapsulation or conjugation of commercially available probes to de novo synthesis This review is limited to reports from the last approximately 5 years that deal with agents that carry two or more species of contrast enhancers Tables summarizing the physical properties from cited articles are included with each major category of probe to facilitate “browsing” by the reader

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Multimodality Imaging Probes: Design and Challenges

Metal complexes as enzyme inhibitors.

A series of core/shell CdSe/Zn1-xMnxS nanoparticles were synthesized for use in dual-mode optical and magnetic resonance (MR) imaging techniques. Mn2+ content was in the range of 0.6−6.2% and varies with the thickness of the shell or amount of Mn2+ introduced to the reaction. These materials showed high quantum yield (QY), reaching 60% in organic solvent. Water-soluble nanoparticles were obtained by capping the core/shell particles with amphiphilic polymer, and the QY values in water reached 21%. These materials also demonstrated high relaxivity with r1 values in the range of 11−18 mM-1 s-1 (at room temperature, 7 T). Both optical and MR imaging were performed on nanoparticles in aqueous solution and applied to cells in culture. The results showed that the QY and manganese concentration in the particles was sufficient to produce contrast for both modalities at relatively low concentrations of nanoparticles.

Angelique Y. Louie

Papers

In vivo visualization of gene expression using magnetic resonance imaging

Multimodality Imaging Probes: Design and Challenges

Metal complexes as enzyme inhibitors.

Core/shell quantum dots with high relaxivity and photoluminescence for multimodality imaging.

Synthesis of 64Cu-Labeled Magnetic Nanoparticles for Multimodal Imaging