Latest developments in molecular tracers for fluorescence image-guided cancer surgery

Hernot, Sophie; Manen, Labrinus van; Debie, Pieterjan; Mieog, J. Sven D.; Vahrmeijer, Alexander L.

doi:10.1016/s1470-2045(19)30317-1

Cited by 310 publications

(292 citation statements)

References 74 publications

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“…Malheureusement, les colorants autorisés actuellement pour la clinique (fluorescéine, bleu de méthylène, ICG, IRD800CW) n'émettent pas dans ces longueurs d'onde et/ou sont des colorants non ciblés [9]. Ces molécules sont très utiles en ophtalmologie [10] et sont même évaluées en chirurgie oncologique, mais elles ne sont malheureusement pas les mieux adaptées [11][12][13]. Les chirurgiens oncologues ont besoin d'agents fluorescents NIR haute performance et ciblés sur les tumeurs pour un guidage optimal de leur geste opératoire [6].…”

Section: La Limite Actuelle : L'agent De Contraste Fluorescentunclassified

“…Les chirurgiens oncologues ont besoin d'agents fluorescents NIR haute performance et ciblés sur les tumeurs pour un guidage optimal de leur geste opératoire [6]. Les agents de contraste fluorescents spécifiques des tumeurs dont deux bilans ont été faits récemment par Debie et Hernot [11] et Hernot et al [12] peuvent se répartir en deux grandes catégories : les agents fluorescents permanents et les agents activables. Cette dernière catégorie exploite (a) certaines spécificités de l'environnement tumoral (acidité, présence d'enzymes, etc.)…”

Section: La Limite Actuelle : L'agent De Contraste Fluorescentunclassified

“…Les nombreuses études précliniques et quelques études cliniques concernant le développement de traceurs fluorescents pour la FGS ont fait l'objet de deux revues récentes [11,12]. Nous ne commenterons ici que les conjugués anticorps-colorant qui sont entrés en étude clinique.…”

Section: Les Conjugués Anticorps-colorants En Cliniqueunclassified

“…Avec de plus en plus de molécules en études cliniques [11,12], dont deux en phase III (NCT03180307 pour vasculaires [42]. Il existe actuellement un consensus pour utiliser des colorants dans le proche infra-rouge (650-900 nm [19,44] ou les nanobodies [45,46], en se fondant sur l'argument qu'une cinétique courte est plus favorable et que de petites entités peuvent pénétrer plus profondément dans les nodules tumoraux.…”

Section: Perspectivesunclassified

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Les anticorps, outils de choix pour la chirurgie guidée par fluorescence

2019

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La chirurgie guidée par fluorescence se développe en clinique depuis plusieurs années. Si l’utilisation de colorants non ciblés peut être utile dans certaines pathologies, des agents de contraste spécifiques sont indispensables en oncologie. Comme le montrent les dernières études cliniques, les anticorps monoclonaux ont toutes les caractéristiques pour jouer un rôle majeur dans ce domaine d’imagerie médicale, à condition que la cible antigénique soit pertinente.

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Section: La Limite Actuelle : L'agent De Contraste Fluorescentunclassified

Section: Les Conjugués Anticorps-colorants En Cliniqueunclassified

Section: Perspectivesunclassified

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Les anticorps, outils de choix pour la chirurgie guidée par fluorescence

2019

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“…Fluorescence imaging has already become a widely used imaging techniques in biomedical research and clinical practice, which can image the structural and functional changes in living organism. [8][9][10][11][12][13] With the discovery of specific biomarkers of lymphatic vessels, the distribution of lymphatic vessels in various tissues and its role in pathological progression is increasingly clear through immunofluorescence imaging. High-resolution imaging techniques including optical coherence tomography and light sheet microscopy let researchers further construct three-dimensional images of lymphatic vasculature system in each organ and provide more accurate and detailed morphological information such as structure, diameter and flow of lymphatic vessels.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances on Fluorescence Imaging of Lymphatic Vasculature System

Li¹,

Li²,

Xiong³

2019

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Lymphatic vasculature system has attracted extensive attention due to its important role in some pathological changes such as lymphedema, immune dysfunction, gut malabsorption and lymph node metastasis, etc. With the continuous development of fluorescence imaging technology, it has been widely used in the study of lymphatic vessels structure, morphology, and function both in preclinical and clinical. Fluorescence imaging can help researchers and clinicians to know the morphological and functional status of lymphatic vessels, explore the role of lymphatic vessels in various lymph-related diseases, and help diagnosis the state of lymphatic vessels in patients and formulate further treatment plan. Herein, we describe the usage and recent advances of fluorescence imaging technology including immune fluorescence imaging, optical coherence tomography, near-infrared fluorescence imaging in ex vivo and in vivo lymphangiography, and discuss the future applications of fluorescence imaging in lymphatic vasculature imaging.

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Targeted Intraoperative Molecular Imaging for Localizing Nonpalpable Tumors and Quantifying Resection Margin Distances

et al. 2021

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IMPORTANCE Complete (R0) resection is the dominant prognostic factor for survival across solid tumor types. Achieving adequate tumor clearance with appropriate margins is particularly difficult in nonpalpable tumors or in situ disease. Previous methods to address this problem have proven time consumptive, impractical, or ineffective. OBJECTIVE To assess the capability of intraoperative molecular imaging (IMI), a novel technology using a fluorescent tracer targeted to malignant cells, to localize visually occult, nonpalpable tumors and quantify margin distances during resection. DESIGN, SETTING, AND PARTICIPANTSThis nonrandomized open-label trial of IMI using a folate receptor-targeted fluorescent tracer enrolled patients between May 2017 and June 2020 at a single referral center. Eligible patients included those with a small (T1) lung lesion suspicious for malignant neoplasms and with radiographic features suggestive of a nonpalpable lesion.INTERVENTIONS Patients were preoperatively infused with a folate receptor-targeted near-infrared tracer. Intraoperatively, surgeons used thoracoscopic visualization and palpation to identify lesions. IMI was performed to detect the lesion in situ, and lesions were imaged ex vivo. Margins were assessed by IMI before comparison with those reported on final histopathologic analysis. MAIN OUTCOMES AND MEASURESThe main outcomes were whether IMI could (1) localize nonpalpable lung lesions in situ and (2) quantify margin distance with comparison with final pathology as the criterion standard. Patient demographic information and lesion characteristics were prospectively recorded. RESULTSOf 40 patients, 26 (65%) were female, and the median (interquartile range) age was 66.5 (62-72) years. Conventional surgical methods localized 22 of 40 lesions (55%), while IMI localized 36 of 40 (90%). Of 18 nonpalpable lesions, 15 (83.3%) were identified by IMI. Both palpable and nonpalpable lesions demonstrated mean signal-to-background ratio more than 2. An IMI margin was able to be calculated for 39 of 40 patients (95%). IMI margins were nearly identical to margins reported on final pathology (R 2 = 0.9593), with median (interquartile range) difference of 1.3 (0.7-2.0) mm. IMI detected 2 margins in nonpalpable tumors that were clinically unacceptable and would have had a high probability of recurrence. CONCLUSIONS AND RELEVANCETo our knowledge, this study presents the first clinical use of IMI for nonpalpable tumors and provides proof of principle for the utility of IMI across the field of surgical oncology in identifying occult disease and tumor-positive margins.

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Latest developments in molecular tracers for fluorescence image-guided cancer surgery

Cited by 310 publications

References 74 publications

Les anticorps, outils de choix pour la chirurgie guidée par fluorescence

Les anticorps, outils de choix pour la chirurgie guidée par fluorescence

Recent Advances on Fluorescence Imaging of Lymphatic Vasculature System

Targeted Intraoperative Molecular Imaging for Localizing Nonpalpable Tumors and Quantifying Resection Margin Distances

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