Intraoperative near-infrared fluorescence imaging of a paraganglioma using methylene blue: A case report

Tummers, Quirijn R.J.G.; Boonstra, Martin C.; Frangioni, John V.; Velde, Cornelis J.H. van de; Vahrmeijer, Alexander L.; Bonsing, Bert A.

doi:10.1016/j.ijscr.2014.12.002

Cited by 31 publications

(26 citation statements)

References 17 publications

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“…They have been used successfully in diagnosing patients with NET using nuclear imaging technologies, such as SPECT or PET, in combination with CT. They have also been used successfully for peptide receptor radionuclide therapy in patients with metastasized disease (2,3), although surgical resection of the tumor tissue, if possible, is the preferred treatment for NET (4,5).…”

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confidence: 99%

Evaluation of a Fluorescent and Radiolabeled Hybrid Somatostatin Analog In Vitro and in Mice Bearing H69 Neuroendocrine Xenografts

et al. 2016

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In the treatment of neuroendocrine tumors (NETs), complete surgical removal of malignancy is generally desirable, because it offers curative results. Preoperative guidance with radiolabeled somatostatin analogs, commonly used for NET diagnosis and preoperative planning, is limited by its low resolution, with the risk that tumor margins and small metastases will be incompletely resected with subsequent recurrence. A single hybrid probe combining radiotracer and optical dye would enable high-resolution optical guidance, also during surgery. In the current study, the hybrid labeled somatostatin analog Cy5-DTPA-Tyr 3 -octreotate (DTPA is diethylene triamine pentaacetic acid) was synthesized and evaluated for its ability to specifically trace NET cells in vitro and in an animal model. The performance of the hybrid tracer was compared with that of octreotate with only radiolabel or only optical label. Methods: The binding affinity and internalization capacity of Cy5-DTPA-Tyr 3 -octreotate were assessed in vitro. Biodistribution profiles and both nuclear and optical in vivo imaging of Cy5-111 In -DTPA-Tyr 3 -octreotate were performed in NET-bearing mice and compared with the performance of 111 In-DTPA-Tyr 3 -octreotate. Results: In vitro studies showed a low receptor affinity and internalization rate for Cy5-DTPA-Tyr 3 -octreotate. The dissociation constant value was 387.7 ± 97.9 nM for Cy5-DTPA-Tyr 3 -octreotate, whereas it was 120.5 ± 18.1 nM for DTPA-Tyr 3 -octreotate. Similarly, receptor-mediated internalization reduced from 33.76% ± 1.22% applied dose for DTPA-Tyr 3 -octreotate to 1.32% ± 0.02% applied dose for Cy5-DTPA-Tyr 3 -octreotate. In contrast, in vivo and ex vivo studies revealed similar tumor uptake values of Cy5-111 In-DTPA-Tyr 3 -octreotate and 111 In -DTPA-Tyr 3 -octreotate (6.93 ± 2.08 and 5.16 ± 1.27, respectively). All organs except the kidneys showed low background radioactivity, with especially low activities in the liver, and high tumor-to-tissue ratios were achieved-both favorable for the tracer's toxicity profile. Hybrid imaging in mice confirmed that the nuclear and fluorescence signals colocalized. Conclusion: The correlation between findings with the optical and the nuclear probes underlines the potential of combining SPECT imaging with fluorescence guidance and shows the promise of this novel hybrid peptide for preoperative and intraoperative imaging of NET.

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confidence: 99%

Evaluation of a Fluorescent and Radiolabeled Hybrid Somatostatin Analog In Vitro and in Mice Bearing H69 Neuroendocrine Xenografts

et al. 2016

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“…This agent exists in the form of several cations in solution and displays far-red fluorescence at low concentrations, with a peak emission wavelength of 688 nm 67,68 . The unique biodistribution and fluorescence properties of methylene blue have been exploited by several investigators to identify vital structures, including the ureters 69 and the parathyroid gland 71–73 (NCT02089542, NCT01598727), as well as cancers such as neuroendocrine insulinomas 74 , fibrous pancreatic tumours 75 , paragangliomas 30 , and para thyroid adenomas 72 , albeit in small case studies; however, the tumour targeting properties of methylene blue remain poorly understood. Methylene blue also exhibits photodynamic properties, with a high efficiency of generating triplet oxygen species when excited by light 76 .…”

Section: Approved Fluorophores For Cancer Imagingmentioning

confidence: 99%

“…Vascular imaging with indocyanine green (ICG) has proven to be a cost-effective imaging modality in assessing perfusion of skin flaps after mastectomy 2,28,29 . Fluorophores have also been used for the detection of cancer, but only a small subset of tumour types can be detected using clinically approved nontargeted fluorophores 9,30 .…”

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confidence: 99%

Beyond the margins: real-time detection of cancer using targeted fluorophores

et al. 2017

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Over the past two decades, synergistic innovations in imaging technology have resulted in a revolution in which a range of biomedical applications are now benefiting from fluorescence imaging. Specifically, advances in fluorophore chemistry and imaging hardware, and the identification of targetable biomarkers have now positioned intraoperative fluorescence as a highly specific real-time detection modality for surgeons in oncology. In particular, the deeper tissue penetration and limited autofluorescence of near-infrared (NIR) fluorescence imaging improves the translational potential of this modality over visible-light fluorescence imaging. Rapid developments in fluorophores with improved characteristics, detection instrumentation, and targeting strategies led to the clinical testing in the early 2010s of the first targeted NIR fluorophores for intraoperative cancer detection. The foundations for the advances that underline this technology continue to be nurtured by the multidisciplinary collaboration of chemists, biologists, engineers, and clinicians. In this Review, we highlight the latest developments in NIR fluorophores, cancer-targeting strategies, and detection instrumentation for intraoperative cancer detection, and consider the unique challenges associated with their effective application in clinical settings.

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“…Importantly, many devices have been designed for the purpose of visualizing optical contrast agents. Currently, a variety of companies manufacture US Food and Drug Administration (FDA)-approved surgical camera systems, such as the Firefly system in the da Vinci Surgical System (Buchs, et al, 2012), the Pinpoint camera (Sherwinter, 2012), the Fluorescence-Assisted Resection and Exploration (FLARE) and Mini-FLARE image-guided surgery systems (Tummers, et al, 2015; Verbeek, et al, 2014; Verbeek, et al, 2013), the Photo Dynamic Eye (PDE) and PDE-neo (Aoki, et al, 2010), the Hyper Eye Medical System (HEMS) (Yoshida, et al, 2012), and the IMAGE1 SPIES near infrared/indocyanine green (NIR/ICG)-system (Schols, et al, 2013). Similarly, there are multiple devices for use in basic science applications and in animal models of disease, including the IVIS, Maestro, Fluobeam, MiroSurge, Lab-FLARE Model R1 Open Space Imaging System and a range of confocal microscopes.…”

Section: Small Molecule and Peptide-based Optical Contrast Agentsmentioning

confidence: 99%

“…While there are a significant number of approved imaging devices, there are no molecularly targeted optical contrast agents that are FDA-approved for clinical use. Thus, all of the current clinical work makes use of non-targeted dyes such as indocyanine green (ICG) (Buchs, et al, 2012; Verbeek, et al, 2014; Yoshida, et al, 2012), methylene blue (MB) (Tummers, et al, 2015; Verbeek, et al, 2013) and fluorescein (Gribar and Hamad, 2007; McGinty, et al, 2003). However, given the availability of imaging devices, efforts to advance optical contrast agents should be a priority, as new agents can be immediately integrated into surgical workflows as they become clinically available.…”

Section: Small Molecule and Peptide-based Optical Contrast Agentsmentioning

confidence: 99%

A Bright Future for Precision Medicine: Advances in Fluorescent Chemical Probe Design and Their Clinical Application

Garland

Yim

Bogyo

2016

Cell Chemical Biology

217

188

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The Precision Medicine Initiative aims to use advances in basic and clinical research to develop therapeutics that selectively target and kill cancer cells. Under the same doctrine of precision medicine, there is an equally important need to visualize these diseased cells to enable diagnosis, facilitate surgical resection and monitor therapeutic response. Therefore, there is a great opportunity for chemists to develop chemically tractable probes that can image cancer in vivo. This review focuses on recent advances in the development of optical probes as well as their current and future applications in the clinical management of cancer. The progress in probe development described here suggests that optical imaging is an important and rapidly developing field of study that encourages continued collaboration between chemists, biologists and clinicians to further refine these tools for interventional surgical imaging, as well as for diagnostic and therapeutic applications.

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Intraoperative near-infrared fluorescence imaging of a paraganglioma using methylene blue: A case report

Cited by 31 publications

References 17 publications

Evaluation of a Fluorescent and Radiolabeled Hybrid Somatostatin Analog In Vitro and in Mice Bearing H69 Neuroendocrine Xenografts

Evaluation of a Fluorescent and Radiolabeled Hybrid Somatostatin Analog In Vitro and in Mice Bearing H69 Neuroendocrine Xenografts

Beyond the margins: real-time detection of cancer using targeted fluorophores

A Bright Future for Precision Medicine: Advances in Fluorescent Chemical Probe Design and Their Clinical Application

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