Fluorescence-Guided Surgery

Nagaya, Tadanobu; Nakamura, Yoriyuki; Choyke, Peter L.; Kobayashi, Hisataka

doi:10.3389/fonc.2017.00314

Cited by 280 publications

(293 citation statements)

References 226 publications

(172 reference statements)

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“…Importantly, we also demonstrate that the MMC is an ideal linker because it produces a bioactive fluorescent analog of 68 Ga-DOTA-TOC and enables quantitative analysis. FGS agent design approaches from our group and others have benefited immensely from the successful first-in-human application of a targeted fluorescent agent by Van Dam and colleagues (21), which represented a major milestone in the field of FGS and played an important role in the development of new dyes and targeted probes (22), optimization of optical imaging systems, and identification of appropriate metrics and validation methods (23,24). Translational initiatives for FGS can be further complemented by combining the strengths of nuclear and optical imaging.…”

Section: Discussionmentioning

confidence: 99%

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Vargas

Kossatz

Voss

et al. 2019

Clinical Cancer Research

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Purpose: Clinically available intraoperative imaging tools to assist surgeons in identifying occult lesions are limited and partially responsible for the high rate of disease recurrence in patients with neuroendocrine tumors (NET). Using the established clinical efficacy of radiolabeled somatostatin analogs as a model, we demonstrate the ability of a fluorescent somatostatin analog to selectively target tumors that overexpress somatostatin receptor subtype-2 (SSTR2) and demonstrate utility for fluorescence-guided surgery (FGS). Experimental Design: A multimodality chelator (MMC) was used as a "radioactive linker" to synthesize the fluorescently labeled somatostatin analog, 67/68 Ga-MMC(IR800)-TOC. In vivo studies were performed to determine the pharmacokinetic profile, optimal imaging time point, and specificity for SSTR2-expressing tissues. Meso-and microscopic imaging of resected tissues and frozen sections were also performed to further assess specific binding, and binding to human NETs was examined using surgical biospecimens from patients with pancreatic NETs. Results: Direct labeling with 67 Ga/ 68 Ga provided quantitative biodistribution analysis that was in agreement with fluorescence data. Receptor-mediated uptake was observed in vivo and ex vivo at the macro-, meso-, and microscopic scales. Surgical biospecimens from patients with pancreatic NETs also displayed receptor-specific agent binding, allowing clear delineation of tumor boundaries that matched pathology findings. Conclusions: The radioactive utility of the MMC allowed us to validate the binding properties of a novel FGS agent that could have a broad impact on cancer outcomes by equipping surgeons with real-time intraoperative imaging capabilities.

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Section: Discussionmentioning

confidence: 99%

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Vargas

Kossatz

Voss

et al. 2019

Clinical Cancer Research

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“…Eventually, fluorescence endomicroscopy traditionally exploits two categories of fluorescent labels, depending on its applicative fields. Indocyanine green, Methylene blue, and Fluorescein can be presently used for clinical applications [5]. Biological applications are compatible with a broader library of fluorophores.…”

Section: Discussionmentioning

confidence: 99%

“…Fiber-optic-based fluorescence endomicroscopes are versatile devices that have found numerous biological and medical applications [1][2][3][4][5]. In contrast to conventional imaging tools, they permit the noninvasive imaging of cells when they are located within hollow tissue tracts or deeply embedded within solid organs [6].…”

Section: Introductionmentioning

confidence: 99%

Simple imaging protocol for autofluorescence elimination and optical sectioning in fluorescence endomicroscopy

Zhang¹,

Chouket²,

Tebo³

et al. 2019

Optica

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Fiber-optic epifluorescence imaging with one-photon excitation benefits from its ease of use, cheap light sources, and full-frame acquisition, which enables it for favorable temporal resolution of image acquisition. However, it suffers from a lack of robustness against autofluorescence and light scattering. Moreover, it cannot easily eliminate the out-offocus background, which generally results in low-contrast images. In order to overcome these limitations, we have implemented fast out-of-phase imaging after optical modulation (Speed OPIOM) for dynamic contrast in fluorescence endomicroscopy. Using a simple and cheap optical-fiber bundle-based endomicroscope integrating modulatable light sources, we first showed that Speed OPIOM provides intrinsic optical sectioning, which restricts the observation of fluorescent labels at targeted positions within a sample. We also demonstrated that this imaging protocol efficiently eliminates the interference of autofluorescence arising from both the fiber bundle and the specimen in several biological samples. Finally, we could perform multiplexed observations of two spectrally similar fluorophores differing by their photoswitching dynamics. Such attractive features of Speed OPIOM in fluorescence endomicroscopy should find applications in bioprocessing, clinical diagnostics, plant observation, and surface imaging.

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“…The standard practice for prostatectomy relies on visual inspection and palpation during classic open surgery. Because the naked eye is more often limited in its ability to differentiate cancer cells versus healthy cells, visual localization of tumor cells and margins using abnormal color and/or morphology is not reliable (10). Moreover, the naked eye cannot detect smaller and early-stage tumors, especially tumors obscured under other healthy tissues.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Novel Prostate-Specific Membrane Antigen-Targeted Near-Infrared Imaging Agent for Fluorescence-Guided Surgery of Prostate Cancer

Kularatne

Thomas

Myers

et al. 2019

Clinical Cancer Research

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The ability to locate and remove all malignant lesions during radical prostatectomy leads not only to prevent biochemical recurrence (BCR) and possible side effects but also to improve the life expectancy of patients with prostate cancer. Fluorescence-guided surgery (FGS) has emerged as a technique that uses fluorescence to highlight cancerous cells and guide surgeons to resect tumors in real time. Thus, development of tumor-specific near-infrared (NIR) agents that target biomarkers solely expressed on prostate cancer cells will enable to assess negative tumor margins and affected lymph nodes. Because PSMA is overexpressed in prostate cancer cells in >90% of the prostate cancer patient population, a prostate-specific membrane antigen (PSMA)-targeted NIR agent (OTL78) was designed and synthesized. Optical properties, and specificity, tumor-to-background ratio (TBR), accomplishment of negative surgical tumor margins using FGS, pharmacokinetics (PKs) properties, and preclinical toxicology of OTL78 were then evaluated in requisite models. OTL78 binds to PSMA-expressing cells with high affinity, concentrates selectively to PSMA-positive cancer tissues, and clears rapidly from healthy tissues with a half-time of 17 minutes. It also exhibits an excellent TBR (5:1) as well as safety profile in animals. OTL78 is an excellent tumor-specific NIR agent for use in fluorescence-guided radical prostatectomy and FGS of other cancers.

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Fluorescence-Guided Surgery

Cited by 280 publications

References 226 publications

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Specific Targeting of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

Simple imaging protocol for autofluorescence elimination and optical sectioning in fluorescence endomicroscopy

Evaluation of Novel Prostate-Specific Membrane Antigen-Targeted Near-Infrared Imaging Agent for Fluorescence-Guided Surgery of Prostate Cancer

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