Intraoperative Detection of Micrometastases in Whole Excised Lymph Nodes Using Fluorescent Paired-Agent Imaging Principles: Identification of a Suitable Staining and Rinsing Protocol

Li, Chengyue; Torres, Veronica C.; He, Yusheng; Xu, Xiaochun; Basheer, Yusairah; Papavasiliou, Georgia; Samkoe, Kimberley S.; Brankov, Jovan G.; Tichauer, Kenneth M.

doi:10.1007/s11307-021-01587-z

Cited by 15 publications

(12 citation statements)

References 40 publications

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“…Integrins are transmembrane signaling receptors that mediate the adhesive properties of epithelial cells and thus modulate cell growth and differentiation. Clinical cancer researchers continue to search for correlations between altered integrin expression and disease progression and a common literature approach is to image histology sections using immunofluorescence microscopy. − PAI is emerging as a sensitive technique for this type of biomarker detection and distribution mapping, − and future research studies will determine the feasibility of PAI protocols that stain tissue sections with the new fluorescent probes developed in this study …”

Section: Resultsmentioning

confidence: 99%

Comparison of cRGDfK Peptide Probes with Appended Shielded Heptamethine Cyanine Dye (s775z) for Near Infrared Fluorescence Imaging of Cancer

Gamage

Schreiber

et al. 2021

ACS Omega

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Previous work has shown that the sterically shielded near-infrared (NIR) fluorescent heptamethine cyanine dye, s775z, with a reactive carboxyl group produces fluorescent bioconjugates with an unsurpassed combination of high photostability and fluorescence brightness. This present contribution reports two new reactive homologues of s775z with either a maleimide group for reaction with a thiol or a strained alkyne group for reaction with an azide. Three cancer-targeting NIR fluorescent probes were synthesized, each with an appended cRGDfK peptide to provide selective affinity for integrin receptors that are overexpressed on the surface of many cancer cells including the A549 lung adenocarcinoma cells used in this study. A set of cancer cell microscopy and mouse tumor imaging experiments showed that all three probes were very effective at targeting cancer cells and tumors; however, the change in the linker structure produced a statistically significant difference in some aspects of the mouse biodistribution. The mouse studies included a mock surgical procedure that excised the subcutaneous tumors. A paired-agent fluorescence imaging experiment co-injected a binary mixture of targeted probe with 850 nm emission, an untargeted probe with 710 nm emission and determined the targeted probe’s binding potential in the tumor tissue. A comparison of pixelated maps of binding potential for each excised tumor indicated a tumor-to-tumor variation of integrin expression levels, and a heterogeneous spatial distribution of integrin receptors within each tumor.

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Section: Resultsmentioning

confidence: 99%

Comparison of cRGDfK Peptide Probes with Appended Shielded Heptamethine Cyanine Dye (s775z) for Near Infrared Fluorescence Imaging of Cancer

Gamage

Schreiber

et al. 2021

ACS Omega

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“…1B), and assuming scattering anisotropy, g, = 0.9. Simulations were carried out making the following assumptions: 100 mW 680 nm and 780 nm lasers, 4% light loss at every optical interface, 100 nM background fluorescence [estimated from experimental work (19)], 30% fluorophore quantum efficiency (at each wavelength), 6-OD absorption of excitation light at fluorescence filters, and 30% quantum efficiency of the camera with camera pixels binned to 0.1 mm size. Fluorescence concentration in 0.2-mm-diameter simulated micrometastases was set to 130 nM for the 780 nm "targeted" imaging agent (assuming a binding potential of 0.3, which would be like that expected in a low-EGFR expressing head and neck cancer cell line ( 22)).…”

Section: Photon Propagation Modelingmentioning

confidence: 99%

“…The approach is to use paired-agent molecular imaging principles-where a control imaging agent is co-administered with a cancer-targeted agent as a means of accounting for delivery variability and nonspecific accumulation of the targeted agent (10,11)-and narrow aperture fluorescence tomography for whole excised node rapid imaging. To date, our group has built a prototype of the narrow aperture fluorescence imaging system that we have coined ADEPT (agent dependent early photon tomography) and demonstrated the ability to detect "micrometastases" in pig nodes (12)(13)(14)(15)(16)(17), and identified a method for staining and rinsing whole excised lymph nodes with our paired imaging agents (18,19). In this work, all the information we have gathered characterizing our system, data analysis procedures, imaging agent properties, and tissue optical properties were used to develop an accurate simulation model to explore the potential accuracy and precision of detecting clinically relevant levels of cancer in excised lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Fluorescence mesoscopic imaging of whole lymph nodes for intraoperative sentinel lymph node biopsy procedures

Tichauer

Rounds

Torres

et al. 2023

Molecular-Guided Surgery: Molecules, Devices, and Applications IX

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An increasing number of cancer surgery protocols are including sentinel lymph node biopsies on the day of resection to stage for non-palpable spread of cancer through tumor draining lymph nodes. The challenge is that often a tumor-positive node will make it necessary to perform an enhanced resection of the lymphatic network, and if lymph node processing is not completed within the timeframe of surgery, then patients may have to be called back for additional surgery or have to undergo amplified chemo or radiation therapy. Our group is working on a rapid lymph node staining and fluorescence tomography system that we call ADEPT to provide surgeons with lymph node biopsy results within 15 min. The aim is to minimize the number of callback surgery or amplified therapy procedures to minimize stress to patients and reduce health care costs. This work predicts, using Monte Carlo photon propagation modeling simulations, that ADEPT has the potential to yield greater than 95% accuracy in detecting the smallest amount of cancer considered clinically relevant withing 15 min of tissue processing and imaging.

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“…This sensor can distinguish diseased from healthy tissue in an estimated 92% of cases. 97 Li et al 98 demonstrated an excellent ability to detect lymph nodes using fluorescent paired-agent imaging. Micrometastases (0.2 mm diameter) can be detected by fluorescent paired-agent imaging with >99% sensitivity and >95% specificity compared to frozen pathology, which has a sensitivity of 20%.…”

Section: Technology For Detecting Micrometastasismentioning

confidence: 99%

Emerging Technologies for the Detection of Cancer Micrometastasis

Mao

Mei

et al. 2022

Technol Cancer Res Treat

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The most efficient way to treat tumors is through surgery. However, many cancer patients have a poor prognosis even when they undergo radical excision at an early stage. Micrometastasis is one of the most critical factors that induced this situation. Undetected micrometastasis can lead to the failure of initial treatment. Therefore, preoperative and intraoperative detection of micrometastasis could have a significant clinical influence on the prognosis and optimal therapy for cancer patients. Additionally, to achieve this goal, researchers have aimed to create more effective detection technologies. Herein, we classify the currently reported micrometastasis detection technologies, introduce some representative samples for each technology, including the limitations, and provide future directions to overcome the limitations.

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Intraoperative Detection of Micrometastases in Whole Excised Lymph Nodes Using Fluorescent Paired-Agent Imaging Principles: Identification of a Suitable Staining and Rinsing Protocol

Cited by 15 publications

References 40 publications

Comparison of cRGDfK Peptide Probes with Appended Shielded Heptamethine Cyanine Dye (s775z) for Near Infrared Fluorescence Imaging of Cancer

Comparison of cRGDfK Peptide Probes with Appended Shielded Heptamethine Cyanine Dye (s775z) for Near Infrared Fluorescence Imaging of Cancer

Fluorescence mesoscopic imaging of whole lymph nodes for intraoperative sentinel lymph node biopsy procedures

Emerging Technologies for the Detection of Cancer Micrometastasis

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