Real-time<i>in vivo</i>imaging of metastatic bone tumors with a targeted near-infrared fluorophore

Lim, Wonbong; Sohn, HongMoon; Ko, Youngjong; Park, Mineon; Kim, Bora; Jo, Daewoong; Jung, Joohee; Yang, Dae Hyeok; Kim, Jangho; Kim, Nam Keun; Kim, Donghwi; Moon, Young Lae; Min, Jung‐Joon; Hyun, Hoon

doi:10.18632/oncotarget.20187

Cited by 18 publications

(16 citation statements)

References 23 publications

(24 reference statements)

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“…The lipophilic NIR cyanine fluorophore ESNF13 was previously developed for the longitudinal monitoring of cell proliferation and differentiation with low cytotoxicity, high optical properties, and low background outside cells. Unlike other tracking techniques, ESNF13 requires facile and simple procedures for intracellular trafficking ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Real-Time Tracking of Ex Vivo-Expanded Natural Killer Cells Toward Human Triple-Negative Breast Cancers

et al. 2018

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IntroductionEx vivo-expanded natural killer (NK) cells are a potential candidate for cancer immunotherapy based on high cytotoxicity against malignant tumor cells. However, a limited understanding of the migration of activated NK cells toward solid tumors is a critical dilemma in the development of effective and adoptive NK cell-based immunotherapy.MethodsEx vivo-expanded NK cells from healthy donors were stained with near-infrared fluorophores at different concentrations. NK cell proliferation and cytotoxicity were assessed using a WST-8 assay, while the expression levels of surface molecules were analyzed by flow cytometry. To investigate the biodistribution of NK cells in both normal and tumor-bearing NSG mice, NK cells labeled with ESNF13 were subjected to NIR fluorescence imaging using the Mini-FLARE imaging system. Finally, mice were sacrificed and histopathological tests were performed in resected organs.ResultsThe signal intensity of ESNF-stained NK cells was long-lasting at 72 h using concentrations as low as 0.04 µM. At a low dose range, ESNF13 did not affect NK cell purity, expression levels of surface receptors, or cytotoxic functions against MDA-MB-231 cancer cells. Ex vivo-expanded NK cells labeled with ESNF13 had a 4-h biodistribution in non-tumor-bearing NSG mice that mainly localized to the lungs immediately after injection and then fully migrated to the kidney after 4 h. In an MDA-MB-231 tumor-bearing NSG mice with extensive metastasis in both lungs, the fluorescence signal was dominant in both lungs and steady at 1, 2, and 4 h post-injection. In a early phase of tumor progression, administered NK cell migrated to the lungs and tumor sites within 30 min post-injection, the signal dominated the tumor site after 1 h, and remained steady at 4 h.ConclusionOptical imaging with NIR fluorophore ESNF13 is a highly sensitive, applicable, and inexpensive method for the real-time tracking of ex vivo-expanded NK cells both in vitro and in vivo. Administered NK cells had different patterns of NK cell distribution and accumulation to the tumor site according to tumor progression in triple-negative breast cancer xenograft models.

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Section: Introductionmentioning

confidence: 99%

Real-Time Tracking of Ex Vivo-Expanded Natural Killer Cells Toward Human Triple-Negative Breast Cancers

et al. 2018

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“…NIR Fluorescence Imaging System : In vivo NIR fluorescence imaging was performed using the Mini‐FLARE imaging system as described previously . Briefly, the system consists of three separate light sources of different wavelengths: a “white” light‐emitting diode (LED) light source, generating 26 600 lux of 400–650 nm light to illuminate the surgical field, and NIR LED light sources, generating Channel #1 (656–678 nm excitation; 689–725 nm emission; 1.08 mW cm −2 fluence rate) and Channel #2 (745–779 nm excitation; 800–848 nm emission; 7.70 mW cm −2 fluence rate).…”

Section: Methodsmentioning

confidence: 99%

“…Near‐infrared (NIR; 650–900 nm) fluorescence imaging is a fast, inexpensive, and nonionizing modality that provides new opportunities for effective diagnostic technology of breast cancer by assessing different types of microcalcifications . Recently, we have developed phosphonated NIR fluorophores binding to HA and CP crystals that exhibit bone tissue‐specific uptake by virtue of structure‐inherent targeting .…”

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confidence: 99%

Rapid Differential Diagnosis of Breast Microcalcification Using Targeted Near‐Infrared Fluorophores

Park

Lim

et al. 2017

Adv Healthcare Materials

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Early detection and differential diagnosis of breast microcalcifications are of significant importance in effective treatment of early breast cancer, because mineral composition of breast calcification is directly associated with different pathological states. However, applying image-based modalities for component identification in breast calcification remains challenging, because no calcification-specific contrast agent is available to distinguish between benign and malignant (type I and type II, respectively) calcifications of breast lesions. In this study, real-time near-infrared (NIR) fluorescence imaging of breast microcalcifications using targeted NIR fluorophores in combination with dual-channel NIR fluorescence imaging system is reported. This strategy can be used to solve major problem in mammography and ultrasonography methods for the differentiation of benign and malignant microcalcifications. Thus, this novel technology shows significant potential for breast cancer diagnosis and image-guided surgery performed with increased precision and efficiency by providing differential diagnosis of breast microcalcifications.

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“…During recent years, more attention has been paid to imaging rare events such as tumor cell dissemination or dormancy with more advanced techniques. For example, real-time in vivo imaging of bone metastatic tumors by near-infrared techniques could be useful in more precise tumor detection in bone, and for detecting small tumors [14]. More precise tumor detection can also be achieved by intravital imaging of bone marrow and tumor cells by two-photon microscopy [15•].…”

Section: Introductionmentioning

confidence: 99%

Novel and Conventional Preclinical Models to Investigate Bone Metastasis

et al. 2019

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Purpose of Review The purpose of this review is to emphasize the use of bone metastasis models in preclinical research. As classical models have been thoroughly discussed in recent reviews, we here highlight the most important aspects from these papers with a special focus on novel models developed during the past 5 years. Recent Findings Preclinical mouse models to study bone metastasis can be divided by cancer cell inoculation techniques (spontaneous, systemic, or local) or by immunological background of the mice (immunodeficient, syngeneic, or humanized). Additionally, novel computational, in vitro co-culture, and humanized bone models have been established. Summary Various models can be used to approach distinct research questions. Understanding limitations of the models is essential when planning a study and interpreting the results. Development of novel models will increase understanding of the complex biology and advance the discovery of new therapies targeting bone metastases.

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Real-timein vivoimaging of metastatic bone tumors with a targeted near-infrared fluorophore

Cited by 18 publications

References 23 publications

Real-Time Tracking of Ex Vivo-Expanded Natural Killer Cells Toward Human Triple-Negative Breast Cancers

Real-Time Tracking of Ex Vivo-Expanded Natural Killer Cells Toward Human Triple-Negative Breast Cancers

Rapid Differential Diagnosis of Breast Microcalcification Using Targeted Near‐Infrared Fluorophores

Novel and Conventional Preclinical Models to Investigate Bone Metastasis

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