Multi-Wavelength Fluorescence in Image-Guided Surgery, Clinical Feasibility and Future Perspectives

Beurden, Florian van; Willigen, Danny M. van; Vojnovic, Borivoj; Oosterom, Matthias N. van; Brouwer, O.R.; Poel, Henk G. van der; Kobayashi, Hisataka; Leeuwen, Fijs W. B. van; Buckle, Tessa

doi:10.1177/1536012120962333

Cited by 44 publications

(40 citation statements)

References 133 publications

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“…While most image-guided surgery studies promote the use of near-infrared (NIR) Cy7 analogues [ 53 , 54 , 56 ], far-red Cy5-labels are also increasingly being applied in clinical trials [ 39 , 57 – 59 ]. In fact, fluorescence-guided surgery trials have been reported for the full fluorescent light spectrum [ 60 ]. Uniquely, in a head-to-head comparison, Cy5 analogues even were shown to outperform Cy7-analogies in terms of signal intensity [ 42 ] and impact on tracer kinetics [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Cy5 analogues, both a free dye and conjugated to a peptide, have shown to have a high fluorescence brightness in the presence of human serum albumin (Additional file 1 : Table SI2; [ 36 , 41 , 61 ]). These factors combined with the fact that most groups are creating tumour-receptor-targeted tracers using NIR Cy7 analogues support the future implementation of multi-wavelength imaging applications, a concept that is gaining traction in the clinic [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

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Intraoperative visualization of nerves using a myelin protein-zero specific fluorescent tracer

et al. 2021

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Background Surgically induced nerve damage is a common but debilitating side effect in oncological surgery. With the aim to use fluorescence guidance to enable nerve-sparing interventions in future surgery, a fluorescent tracer was developed that specifically targets myelin protein zero (P0). Results Truncated homotypic P0 protein-based peptide sequences were C-terminally functionalized with the far-red cyanine dye Cy5. The lead compound Cy5-P0101–125 was selected after initial solubility, (photo)physical and in vitro evaluation (including P0-blocking experiments). Cy5-P0101–125 (KD = 105 ± 17 nM) allowed in vitro and ex vivo P0-related staining. Furthermore, Cy5-P0101–125 enabled in vivo fluorescence imaging of the Sciatic nerve in mice after local intravenous (i.v.) administration and showed compatibility with a clinical fluorescence laparoscope during evaluation in a porcine model undergoing robot-assisted surgery. Biodistribution data revealed that i.v. administered [111In]In-DTPA-P0101–125 does not enter the central nervous system (CNS). Conclusion P0101–125 has proven to be a potent nerve-specific agent that is able to target P0/myelin under in vitro, ex vivo, and in vivo conditions without posing a threat for CNS-related toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intraoperative visualization of nerves using a myelin protein-zero specific fluorescent tracer

et al. 2021

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“…While NIR-based fluorescence imaging is popular amongst many that pursue the development of new tracers for fluorescence-guided surgery, far-red Cy5-based tracers are also on the rise in clinical trials, e.g., based on EMI-137 [ 8 , 9 , 25 ] and cRGDY-PEG-Cy5.5-nanoparticles [ 6 ]. In fact, visible dyes, such as fluorescein and pPXi, have been widely applied in clinical trials [ 31 ]. Beyond that, literature even suggests that fluorescent emissions in different portions of the fluorescent spectrum can complement each other in multi-wavelength fluorescence imaging [ 26 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, visible dyes, such as fluorescein and pPXi, have been widely applied in clinical trials [ 31 ]. Beyond that, literature even suggests that fluorescent emissions in different portions of the fluorescent spectrum can complement each other in multi-wavelength fluorescence imaging [ 26 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data

Buckle

Alphen

Oosterom

et al. 2021

Cancers

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Intraoperative tumor identification (extension/margins/metastases) via receptor-specific targeting is one of the ultimate promises of fluorescence-guided surgery. The translation of fluorescent tracers that enable tumor visualization forms a critical component in the realization of this approach. Ex vivo assessment of surgical specimens after topical tracer application could help provide an intermediate step between preclinical evaluation and first-in-human trials. Here, the suitability of the c-Met receptor as a potential surgical target in oral cavity cancer was explored via topical ex vivo application of the fluorescent tracer EMI-137. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In-house developed image processing software allowed video-rate assessment of the tumor-to-background ratio (TBR). Fluorescence imaging results were related to standard pathological evaluation and c-MET immunohistochemistry. After incubation with EMI-137, 9/10 tumors were fluorescently illuminated. Immunohistochemistry revealed c-Met expression in all ten specimens. Non-visualization could be linked to a more deeply situated lesion. Tumor assessment was improved via video representation of the TBR (median TBR: 2.5 (range 1.8–3.1)). Ex vivo evaluation of tumor specimens suggests that c-Met is a possible candidate for fluorescence-guided surgery in oral cavity cancer.

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“…The translational character of the findings is underscored by: 1) the proven utility of the DROP-IN concept in prostate-cancer surgery (sentinel nodetargeting with (ICG)-99m Tc-nanacolloid (2), and PSMA-targeting with 99m Tc-PSMA ( 5)), 2) the use of medical-grade fluorescent materials as markers, 3) the use of the clinically approved Firefly camera and declipseSPECT navigation system, and 4) a proof-of-concept in porcine surgery. Obviously, the concept could in the future be disseminated to alternative indications for which 125 I, 99m Tc, or 111 In-based radioguided surgery approaches have been reported (1), or even alternative multi-color fluorescence approaches (16).…”

Section: Discussionmentioning

confidence: 99%

Optical Navigation of the Drop-In γ-Probe as a Means to Strengthen the Connection Between Robot-Assisted and Radioguided Surgery

et al. 2021

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Rationale: With translation of the DROP-IN gamma probe, radioguidance has advanced into laparoscopic robot-assisted surgery. 'GPS-like' navigation further enhances the symbiosis between nuclear medicine and surgery. Therefore, we developed a fluorescence-video-based tracking method that integrates the DROP-IN with navigated-robotic surgery.Methods: Fluorescent markers, integrated into the DROP-IN, were automatically detected using a daVinci Firefly laparoscope. Subsequently, a declipseSPECT-navigation platform calculated the DROP-IN's location within the surgical field. Using a phantom (n=3), we pursued robotic-navigation on single-photon emission computed tomography/computed tomography (SPECT/CT), while intraoperative feasibility was validated during porcine surgery (n=4).Results: Video-based tracking allowed for navigation of the DROP-IN towards all lesions detected on SPECT/CT (external-iliac and common-iliac artery regions). Augmented-reality visualization in the surgical console, indicated the distance to these lesions in real-time, confirmed by the DROP-IN read-out. Porcine surgery underlined the feasibility of the concept. Conclusions:Optical navigation of a DROP-IN probe provides a next step towards connecting nuclearmedicine with robotic surgery.

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Multi-Wavelength Fluorescence in Image-Guided Surgery, Clinical Feasibility and Future Perspectives

Cited by 44 publications

References 133 publications

Intraoperative visualization of nerves using a myelin protein-zero specific fluorescent tracer

Intraoperative visualization of nerves using a myelin protein-zero specific fluorescent tracer

Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer—Initial Proof of Concept Data

Optical Navigation of the Drop-In γ-Probe as a Means to Strengthen the Connection Between Robot-Assisted and Radioguided Surgery

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