Optical molecular imaging and its emerging role in colorectal cancer

Abstract

Sheth RA, Mahmood U. Optical molecular imaging and its emerging role in colorectal cancer. Am J Physiol Gastrointest Liver Physiol 299: G807-G820, 2010. First published July 1, 2010; doi:10.1152/ajpgi.00195.2010.-Colorectal cancer remains a major cause of morbidity and mortality in the United States. The advent of molecular therapies targeted against specific, stereotyped cellular mutations that occur in this disease has ushered in new hope for treatment options. However, key questions regarding optimal dosing schedules, dosing duration, and patient selection remain unanswered. In this review, we describe how recent advances in molecular imaging, specifically optical molecular imaging with fluorescent probes, offer potential solutions to these questions. We begin with an overview of optical molecular imaging, including discussions on the various methods of design for fluorescent probes and the clinically relevant imaging systems that have been built to image them. We then focus on the relevance of optical molecular imaging to colorectal cancer. We review the most recent data on how this imaging modality has been applied to the measurement of treatment efficacy for currently available as well as developmental molecularly targeted therapies. We then conclude with a discussion on how this imaging approach has already begun to be translated clinically for human use. cancer genetics; animal studies; endoscopy; fluorescence MOLECULAR IMAGING IS A RAPIDLY growing field in diagnostic medicine that has the potential to make a significant impact in the manner in which disease is diagnosed and treated (51,57,80). The term molecular imaging can be defined as any imaging modality that allows for the in vivo visualization and characterization of biological processes that occur on a cellular or subcellular scale. Whereas previous technologies have focused on defining disease on the basis of structure and morphology, molecular imaging seeks to reveal the biochemical underpinnings and intracellular pathways that drive disease development and progression. With the recent revolutionary advances in knowledge of the molecular mechanisms of pathological processes, clinicians enjoy now an unprecedented degree of understanding of the nature of disease (126); molecular imaging as a discipline seeks to capitalize on this understanding to develop clinically translatable imaging tools to perform molecular assessments of disease.Molecular imaging promises to provide several advantages over current clinical imaging modalities (57). First is the possibility of earlier disease detection (125). Because molecular imaging techniques evaluate for cellular perturbations rather than physical abnormalities, these approaches can theoretically identify disease states at an earlier stage in development and before they manifest anatomically. Moreover, since molecular imaging methods detect functional variations in tissue rather than structural changes, they are able to focally highlight lesions with very high target-to-background ratios. Another potentia...

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“…Depending on the nature of the study OI probes may be non-targeted, targeted or activatable as described by Sheth and Mahmood [20]. Targeted OI probes (e.g.…”