Probe‐based fluorescence dosimetry of an antibody‐dye conjugate to identify head and neck cancer as a first step to fluorescence‐guided tissue preselection for pathological assessment

Nishio, Naoki; Keulen, Stan van; Berg, Nynke S. van den; Lu, Guolan; LaRochelle, Ethan; Davis, Scott C.; Martin, Brock A.; Fakurnejad, Shayan; Zhou, Quan; Birkeland, Andrew C.; Kaplan, Michael; Divi, Vasu; Colevas, A. Dimitrios; Pogue, Brian W.; Rosenthal, Eben L.

doi:10.1002/hed.25964

Cited by 7 publications

(2 citation statements)

References 28 publications

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“…To accommodate the wide range of interpatient fluorescence signal, minimal ambient light and the lowest imaging gain allowing tumor detection via fluorescence are recommended to maximize tumor-specific visual contrast in open-field intraoperative imaging, extending findings from previous phantom studies ( 12 , 13 ). Although only a few fluorescence peaks were sampled for pathologic assessment of head-and-neck cancer in previous studies ( 10 , 14 ), tissue surface fluorescent contrast was comprehensively characterized against margin distance in our study to identify tumor-to-background ratio cutoffs for detecting positive and close resection margins across 3 malignancies.…”

Section: Discussionmentioning

confidence: 92%

Factors for Differential Outcome Across Cancers in Clinical Molecule-Targeted Fluorescence Imaging

Zhou

Berg²,

Kang³

et al. 2022

J Nucl Med

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Clinical imaging performance using a fluorescent antibody was compared across 3 cancers to elucidate physical and biologic factors contributing to differential translation of epidermal growth factor receptor (EGFR) expression to macroscopic fluorescence in tumors. Methods: Thirty-one patients with high-grade glioma (HGG, n 5 5), head-and-neck squamous cell carcinoma (HNSCC, n 5 23), or lung adenocarcinoma (LAC, n 5 3) were systemically infused with 50 mg of panitumumab-IRDye800 1-3 d before surgery. Intraoperative open-field fluorescent images of the surgical field were acquired, with imaging device settings and operating room lighting conditions being tested on tissue-mimicking phantoms. Fluorescence contrast and margin size were measured on resected specimen surfaces. Antibody distribution and EGFR immunoreactivity were characterized in macroscopic and microscopic histologic structures. The integrity of the blood-brain barrier was examined via tight junction protein (Claudin-5) expression with immunohistochemistry.Stepwise multivariate linear regression of biologic variables was performed to identify independent predictors of panitumumab-IRDye800 concentration in tissue. Results: Optimally acquired at the lowest gain for tumor detection with ambient light, intraoperative fluorescence imaging enhanced tissue-size dependent tumor contrast by 5.2-fold, 3.4-fold, and 1.4-fold in HGG, HNSCC, and LAC, respectively. Tissue surface fluorescence target-to-background ratio correlated with margin size and identified 78%-97% of at-risk resection margins ex vivo. In 4-mm-thick tissue sections, fluorescence detected tumor with 0.85-0.89 areas under the receiver-operating-characteristic curves. Preferential breakdown of blood-brain barrier in HGG improved tumor specificity of intratumoral antibody distribution relative to that of EGFR (96% vs. 80%) despite its reduced concentration (3.9 ng/mg of tissue) compared with HNSCC (8.1 ng/mg) and LAC (6.3 ng/mg). Cellular EGFR expression, tumor cell density, plasma antibody concentration, and delivery barrier were independently associated with local intratumoral panitumumab-IRDye800 concentration, with 0.62 goodness of fit of prediction. Conclusion: In multicancer clinical imaging of a receptor-ligand-based molecular probe, plasma antibody concentration, delivery barrier, and intratumoral EGFR expression driven by cellular biomarker expression and tumor cell density led to heterogeneous intratumoral antibody accumulation and spatial distribution whereas tumor size, resection margin, and intraoperative imaging settings substantially influenced macroscopic tumor contrast.

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Section: Discussionmentioning

confidence: 92%

Factors for Differential Outcome Across Cancers in Clinical Molecule-Targeted Fluorescence Imaging

Zhou

Berg²,

Kang³

et al. 2022

J Nucl Med

Self Cite

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show abstract

“…To accommodate a wide intraoperative signal range, minimal ambient light and the lowest imaging gain that allow tumor detection should be adopted to facilitate adoption and standardization of intraoperative protocols across institutions. This was an extension of our prior studies to characterize open-field imaging contrast with panitumumab-IRDye800 phantoms [25, 26].…”

Section: Discussionmentioning

confidence: 93%

Applications of fluorescence-guided surgery across multiple tumor types using a near-infrared labeled EGFR antibody

Zhou

Berg

Kang

et al. 2021

Preprint

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Background As receptor-ligand based strategies emerge for surgical imaging, the relative importance of receptor expression in different tumor types is unknown. Near-infrared (NIR) labeled epidermal growth factor receptor (EGFR) antibody, panitumumab-IRDye800, was evaluated across three cancers to demonstrate its clinical utilities and a holistic analysis framework. Methods Thirty-one patients diagnosed with high-grade glioma (HGG, n=5, NCT03510208), head and neck squamous cell carcinoma (HNSCC, n=23, NCT02415881) or lung adenocarcinoma (LAC, n=3, NCT03582124) received systemic administration of 50 mg panitumumab-IRDye800 days prior to surgery. Intraoperative NIR laparoscopic or open-field images of the surgical field were acquired and tissue mimicking phantoms were constructed to identify optimal imaging conditions. Margin distance was correlated to fluorescence on resected specimen surface. Panitumumab-IRDye800 distribution was registered to histology in fixed tissue sections. Immunohistochemistry characterized EGFR expression. Results Intraoperative NIR imaging enhanced tumor contrast against surrounding healthy tissue by 5.2-fold, 3.4-fold and 1.4-fold in HGG, HNSCC and LAC, respectively. Imaging quality was optimal at the lowest gain possible under ambient light. Ex vivo NIR fluorescence identified 78-97% of at-risk resection margins, with 72-92% sensitivity and 67-96% specificity for tumor in fixed tissue sections. Intratumoral panitumumab-IRDye800 concentration correlated with total tumoral EGFR expression (HGG > HNSCC > LAC) and delivery barrier. Cellular EGFR expression (80%) and tumor cell density (3000 cells/mm2) was highest in HGG. Conclusions In multiple tumor types, EGFR-targeting in fluorescence-guided surgery translated to enhanced macroscopic tumor contrast and successful margin assessment despite disparate tumor cell density and heterogeneous delivery of pantimumab-IRDye800.

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Identification of Optimal Tissue-Marking Dye Color for Pathological Evaluation in Fluorescence Imaging Using IRDye800CW

Kondo,

Nishio,

Park

et al. 2023

Mol Imaging Biol

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Probe‐based fluorescence dosimetry of an antibody‐dye conjugate to identify head and neck cancer as a first step to fluorescence‐guided tissue preselection for pathological assessment

Cited by 7 publications

References 28 publications

Factors for Differential Outcome Across Cancers in Clinical Molecule-Targeted Fluorescence Imaging

Factors for Differential Outcome Across Cancers in Clinical Molecule-Targeted Fluorescence Imaging

Applications of fluorescence-guided surgery across multiple tumor types using a near-infrared labeled EGFR antibody

Identification of Optimal Tissue-Marking Dye Color for Pathological Evaluation in Fluorescence Imaging Using IRDye800CW

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