Biochromoendoscopy: molecular imaging with capsule endoscopy for detection of adenomas of the GI tract

Zhang, Howard; Morgan, Douglas R.; Cecil, Gerald; Burkholder, Adam; Ramocki, Nicole M.; Scull, Brooks; Lund, P. Kay

doi:10.1016/j.gie.2008.02.023

Cited by 32 publications

(20 citation statements)

References 20 publications

(28 reference statements)

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“…Therefore, we are unable to attribute the observed fluorescent signals to specific tissues associated with PTOA development. However, each of these fluorescent activatable probes has been extensively validated and compared to histological standards [12–19], and in particular have been validated for studies of musculoskeletal tissues [20–23], therefore we are confident that the fluorescent signals are indicative of cellular processes at the level of the whole joint. Our future studies will utilize histological techniques to further characterize the specific tissues in which these fluorescent signals originate following traumatic joint injury using this animal model.…”

Section: Discussionmentioning

confidence: 99%

“…These optical tracers are fluorescently quenched until a linker domain is cleaved by a specific protease of interest, which then produces a robust fluorescent signal. These techniques have been extensively validated and used in studies of cancer [12–15] and atherosclerosis [16–19], but are also potentially useful for studies of the musculoskeletal system to measure markers of inflammation and matrix degradation (cathepsin proteases and matrix metalloproteinases (MMPs)) and bone turnover (cathepsin K), which have vital roles in OA progression. Commercially available fluorescent activatable probes have been validated for use in musculoskeletal applications [20–23].…”

Section: Introductionmentioning

confidence: 99%

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In vivo fluorescence reflectance imaging of protease activity in a mouse model of post-traumatic osteoarthritis

Satkunananthan

Anderson

Jesus

et al. 2014

Osteoarthritis and Cartilage

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Objective Traumatic joint injuries initiate a surge of inflammatory cytokines and proteases that may contribute to cartilage and subchondral bone degeneration. Detecting these early biological processes in animal models of post-traumatic osteoarthritis (PTOA) typically involves ex vivo analysis of blood serum or synovial fluid biomarkers, or destructive histological analysis of the joint. In this study, we used in vivo fluorescence reflectance imaging (FRI) to quantify protease activity, matrix metalloproteinase (MMP) activity, and Cathepsin K activity in mice following ACL rupture. We hypothesized that these processes would be elevated at early time points following traumatic joint injury (1–14 days), but would return to control levels at later time points (4–8 weeks). Design Mice were injured via tibial compression overload, and FRI imaging was performed at multiple time points from 1–56 days after injury using commercially available activatable fluorescent tracers to quantify protease activity, MMP activity, and cathepsin K activity in injured vs. uninjured knees. PTOA was assessed at 56 days post-injury using micro-computed tomography and whole-joint histology. Results Protease activity, MMP activity, and cathepsin K activity were all significantly increased in injured knees relative to uninjured knees at all time points, peaking at 1–7 days post-injury, then decreasing at later time points while still remaining elevated relative to controls. Conclusions This study establishes FRI imaging as a reliable method for in vivo quantification of early biological processes in a translatable mouse model of PTOA, and provides crucial information about the time course of inflammation and biological activity following joint injury. These data may inform future studies aimed at targeting early inflammation to reduce the development of PTOA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivo fluorescence reflectance imaging of protease activity in a mouse model of post-traumatic osteoarthritis

Satkunananthan

Anderson

Jesus

et al. 2014

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

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“…During colonoscopy after orthotopic tumor induction, white light and NIR images could be displayed simultaneously, and pseudocolored overlay images were constructed at real time to assist in the detection of small lesions. Such imaging has also been performed with capsule endoscopy(12). In a proof-of-principle approach, a commercially available capsule has been equipped with a filter device capable of NIR imaging in addition to white light imaging.…”

Section: Preclinical and Clinical Studies Using Molecular Imaging In mentioning

confidence: 99%

Molecular Imaging in Gastrointestinal Endoscopy

2010

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Molecular imaging is a rapidly growing new discipline in gastrointestinal endoscopy. It uses the molecular signature of cells for minimally-invasive, targeted imaging of gastrointestinal pathologies. Molecular imaging comprises wide field techniques for the detection of lesions and microscopic techniques for in vivo characterization. Exogenous fluorescent agents serve as molecular beacons and include labeled peptides and antibodies, and probes with tumor-specific activation. Most applications have aimed at improving the detection of gastrointestinal neoplasia with either prototype fluorescence endoscopy or confocal endomicroscopy, and first studies have translated encouraging results from rodent and tissue models to endoscopy in humans. Even with the limitations of the currently used approaches, molecular imaging has the potential to greatly impact on future endoscopy in gastroenterology.

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“…The high target-to-background ratios generated by fluorescence probes, as well as the tissue penetration of fluorescent NIR photons, may augment our ability to visualize adenomas through thin mucosal folds. Also, flat lesions, which more commonly develop in patients with inflammatory bowel disease, are well identified via protease-activatable probes and can be differentiated from the inflammatory milieu in which they tend to arise (133).…”

Section: Improved Detection Of Colorectal Cancermentioning

confidence: 99%

“…A recent randomized controlled trial showed that conventional capsule endoscopy is inferior to colonoscopy for colorectal cancer screening (118). However, Zhang et al (133) have performed a proof-of-principle experiment using optical molecular imaging to potentially increase the sensitivity and specificity of capsule endoscopy for adenoma detection (1). After injecting APC Min/ϩ mice with a protease-activatable probe, they harvested the colon and fixed it onto a stage that steadily translated the colon under an optical setup that comprised of a clinical capsule endoscope and NIR filters.…”

Section: Potential For Clinical Translationmentioning

confidence: 99%

Optical molecular imaging and its emerging role in colorectal cancer

Sheth

Mahmood

2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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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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Biochromoendoscopy: molecular imaging with capsule endoscopy for detection of adenomas of the GI tract

Abstract: We demonstrate proof of the principle that biochromoendoscopy-CE combined with molecular probes--provides a novel approach that differentiates adenomas from benign polyps and inflammatory lesions.

Cited by 32 publications

References 20 publications

In vivo fluorescence reflectance imaging of protease activity in a mouse model of post-traumatic osteoarthritis

In vivo fluorescence reflectance imaging of protease activity in a mouse model of post-traumatic osteoarthritis

Molecular Imaging in Gastrointestinal Endoscopy

Optical molecular imaging and its emerging role in colorectal cancer

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