Optical Imaging of Cancer-Related Proteases Using Near-Infrared Fluorescence Matrix Metalloproteinase-Sensitive and Cathepsin B-Sensitive Probes

Yhee, Ji Young; Kim, Sun Ah; Koo, Heebeom; Son, Sohee; Ryu, Jee Hoon; Youn, In Chan; Choi, Kuiwon; Kwon, Ick Chan; Kim, Kwangmeyung

doi:10.7150/thno.3716

Cited by 67 publications

(47 citation statements)

References 34 publications

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“…Metastasis is a complicated progress with multi-factors and multi-step, coming down to angiogenesis [22], tumor microenvironment [23] and regulated by various cell growth factors [24]. In our study, we established a reliable metastatic model using H1299 lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

A transferrin-target magnetic/fluorescent dual-mode probe significantly enhances the diagnosis of non-small cell lung cancer

Cai

Cao

et al. 2016

Oncotarget

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To enhance the diagnosis of non-small cell lung cancer (NSCLC), we prepared a dual-modal probe Cy5.5-Tf-Gd-DTPA. Gd-DTPA and near-infrared (NIR) dyes were conjugated to holo-Transferrin (Tf) sequentially, the result of ICP-AES and UV showed 25 Gd ions and 1 Cy5.5 could be loaded per protein, respectively. The calculated longitudinal relaxivity R1 of Cy5.5-Tf-DTPA-Gd was 4.21 mM−1S−1 per Gd while that of Magnevist (Gd-DTPA) was only 4.02 mM−1S−1. Confocal laser scanning microscopy and immunohistochemical analyses revealed that the Cy5.5-Tf-DTPA-Gd was localized and accumulated in cytoplasmic vesicles; the cell toxicity assay showed no apparent toxicity. MR and NIR imaging of mice with subcutaneous H1299 xenografte tumors following intravenous injection of Cy5.5-Tf-DTPA-Gd revealed a strong positive contrast of the tumors, which caused a longer lasting enhancement of the MRI signal and fluorescence signal. Taken together, these studies indicate that Cy5.5-Tf-DTPA-Gd could be a good agent for MR/NIRF dual mode applications to detect both tumor in situ and its metastasis.

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Section: Discussionmentioning

confidence: 99%

A transferrin-target magnetic/fluorescent dual-mode probe significantly enhances the diagnosis of non-small cell lung cancer

Cai

Cao

et al. 2016

Oncotarget

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“…Although both resulted in tumor specific fluorescence of transplanted subcutaneous tumor nodules, signal from the MMP-sensitive probe peaked about 3 hours after injection and decayed more quickly than signal from the cathepsin B-sensitive probe which peaked at 6 hours after injection. Differences of background fluorescence detected in normal organs was also noted (41). …”

Section: Optical Imagingmentioning

confidence: 89%

Tailoring Adjuvant Radiation Therapy by Intraoperative Imaging to Detect Residual Cancer

Whitley

Weissleder

Kirsch

2015

Seminars in Radiation Oncology

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For many solid cancers, radiation therapy is offered as an adjuvant to surgical resection in order to lower rates of local recurrence and improve survival. However, a subset of patients treated with surgery alone will not have a local recurrence. Currently, there is no way to accurately determine which patients have microscopic residual disease in the tumor bed after surgery and therefore are most likely to benefit from adjuvant radiation therapy. To address this problem, a number of technologies have been developed to try to improve margin assessment of resected tissue and to detect residual cancer in the tumor bed. Moreover, some of these approaches have been translated from the preclinical arena into clinical trials. Here, we review different types of intraoperative molecular imaging systems for cancer. Optical imaging techniques like epi-illumination, fluorescence molecular tomography and optoacoustic imaging can be coupled with exogenous fluorescent imaging probes that accumulate in tumors passively via the enhanced permeability and retention effect or are targeted to tumor tissues based on affinity or enzyme activity. In these approaches, detection of fluorescence in the tumor bed may indicate residual disease. Protease activated probes have generated great interest because of their potential for leading to high tumor to normal contrast. Recently, the first Phase I clinical trial to assess the safety and activation of a protease activated probe was conducted. Spectroscopic methods like radiofrequency spectroscopy and Raman spectroscopy, which are based on energy absorption and scattering respectively, have also been tested in humans and are able to distinguish between normal and tumors tissues intraoperatively. Most recently, multi-modal contrast agents have been developed that target tumors and contain both fluorescent dyes and MRI contrast agents, allowing for preoperative planning and intraoperative margin assessment with a single contrast agent. Further clinical testing of these various intraoperative imaging approaches may lead to more accurate methods for margin assessment and the intraoperative detection of microscopic residual disease, which could guide further resection and the use of adjuvant radiation therapy.

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“…These probes can also be used to determine the proximity of the donor and acceptor within a cell. Using this method, many proteases including MMPs [35–39] and cathepsin B [38] have been visualized in live cancer cells. For more detailed descriptions of FRET-based protease probes including dye quenched protein substrates, please see Dive et al [25] and Hu et al [40].…”

Section: Protease-targeted Probes For Live-cell Imagingmentioning

confidence: 99%

Pathomimetic cancer avatars for live-cell imaging of protease activity

Heyza

Sloane

2016

Biochimie

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Proteases are essential for normal physiology as well as multiple diseases, e.g., playing a causative role in cancer progression, including in tumor angiogenesis, invasion, and metastasis. Identification of dynamic alterations in protease activity may allow us to detect early stage cancers and to assess the efficacy of anti-cancer therapies. Despite the clinical importance of proteases in cancer progression, their functional roles individually and within the context of complex protease networks have not yet been well defined. These gaps in our understanding might be addressed with: 1) accurate and sensitive tools and methods to directly identify changes in protease activities in live cells, and 2) pathomimetic avatars for cancer that recapitulate in vitro the tumor in the context of its cellular and non-cellular microenvironment. Such avatars should be designed to facilitate mechanistic studies that can be translated to animal models and ultimately the clinic. Here, we will describe basic principles and recent applications of live-cell imaging for identification of active proteases. The avatars optimized by our laboratory are three-dimensional (3D) human breast cancer models in a matrix of reconstituted basement membrane (rBM). They are designated mammary architecture and microenvironment engineering (MAME) models as they have been designed to mimic the structural and functional interactions among cell types in the normal and cancerous human breast. We have demonstrated the usefulness of these pathomimetic avatars for following dynamic and temporal changes in cell:cell interactions and quantifying changes in protease activity associated with these interactions in real-time (4D). We also briefly describe adaptation of the avatars to custom-designed and fabricated tissue architecture and microenvironment engineering (TAME) chambers that enhance our ability to analyze concomitant changes in the malignant phenotype and the associated tumor microenvironment.

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Optical Imaging of Cancer-Related Proteases Using Near-Infrared Fluorescence Matrix Metalloproteinase-Sensitive and Cathepsin B-Sensitive Probes

Cited by 67 publications

References 34 publications

A transferrin-target magnetic/fluorescent dual-mode probe significantly enhances the diagnosis of non-small cell lung cancer

A transferrin-target magnetic/fluorescent dual-mode probe significantly enhances the diagnosis of non-small cell lung cancer

Tailoring Adjuvant Radiation Therapy by Intraoperative Imaging to Detect Residual Cancer

Pathomimetic cancer avatars for live-cell imaging of protease activity

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