Enzymatically Activatable Diagnostic Probes
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.Current pharmaceutical biotechnology (Impact Factor: 2.51). 01/2012; 13(4):523-36. DOI: 10.2174/138920112799436339
Molecular imaging of disease development, progression and treatment is seen as key to further advancement in the understanding and triumph over illness. The role of enzymes is to catalyze the biochemical reactions that help regulate health, and when dysregulated in complex organisms lead to or indicate disease. The ability to image the action of these proteins for diagnostic purposes opens a window for the researcher and clinician to witness specifc molecular events in vitro and in vivo. Such probes have been developed and deployed for the optical, radionuclide and magnetic resonance modalities and offer significant benefits over conventional agents. The signal of enzymatically-activated probes is regulated by the specific activity of the desired enzyme. This allows for a higher signal to background ratio over non-specific and targeted agents. It also enables the modulation of contrast agent distribution (and even cellular accumulation) following enzymatic activity. This review summarizes the strategies and probes in development and use in this emergent field of molecular imaging, with a particular focus on the research and medical relevance of these advances.
- [Show abstract] [Hide abstract]
ABSTRACT: Anthracycline cytostatics can be observed at the level of organelles, cells and whole organisms due to their fluorescent properties. Imaging techniques based on detection of fluorescence can be used not only for observation of drug interaction with tumor cells, but also for targeting therapy of tumors with nanoparticles containing anthracycline cytostatics. Doxorubicin and daunorubicin, enclosed in liposomes, as representatives of nanoparticles suitable for targeted therapy, are used in clinical practice. The main advantage of liposomal drugs is to reduce the side effects due to differences in pharmacokinetics and distribution of the drug in the body. Due to the fact that all biological mechanisms of action of anthracycline drugs are not still fully understood, modern imaging techniques offer tool for in vivo studies of these mechanisms. Key words: nanomedicine - cytostatic agents - drug delivery systems - doxorubicin - liposomes.
- [Show abstract] [Hide abstract]
ABSTRACT: In the era of personalized medicine, there is an urgent need for in vivo techniques able to sensitively detect and quantify molecular activities. Sensitive imaging of gamma rays is widely used; however, radioactive decay is a physical constant, and its signal is independent of biological interactions. Here, we introduce a framework of previously uncharacterized targeted and activatable probes that are excited by a nuclear decay-derived signal to identify and measure molecular signatures of disease. We accomplished this by using Cerenkov luminescence, the light produced by β-particle-emitting radionuclides such as clinical positron emission tomography (PET) tracers. Disease markers were detected using nanoparticles to produce secondary Cerenkov-induced fluorescence. This approach reduces background signal compared to conventional fluorescence imaging. In addition to tumor identification from a conventional PET scan, we demonstrate the medical utility of our approach by quantitatively determining prognostically relevant enzymatic activity. This technique can be applied to monitor other markers and represents a shift toward activatable nuclear medicine agents.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.