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

Zhou, Quan

van den Berg, Nynke S

Kang, Wenying

Pei, Jacqueline

Nishio, Naoki

van Keulen, Stan

Engelen, Myrthe A

Lee, Yu-Jin

Hom, Marisa

Vega Leonel, Johana CM

Hart, Zachary

Vogel, Hannes

Cayrol, Romain

Martin, Brock A

Roesner, Mark

Shields, Glenn

Lui, Natalie

Gephart, Melanie Hayden

Raymundo, Roan C

Yi, Grace

Granucci, Monica

Grant, Gerald A

Li, Gordon

Rosenthal, Eben L

2023-07-06T17:17:11Z

2023-07-06T17:17:11Z

2022-11

2023-07-06T17:17:09Z

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), head-and-neck squamous cell carcinoma (HNSCC, n = 23), or lung adenocarcinoma (LAC, n = 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-μm-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.

jnumed.121.263674

0161-5505

1535-5667

https://hdl.handle.net/10161/28319

eng

Society of Nuclear Medicine

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

10.2967/jnumed.121.263674

Cell Line, Tumor

Humans

Head and Neck Neoplasms

Optical Imaging

ErbB Receptors

Margins of Excision

Squamous Cell Carcinoma of Head and Neck

Panitumumab

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

Journal article

Grant, Gerald A|0000-0002-2651-4603

1693

1700

11

Duke

School of Medicine

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Neurobiology

Duke Cancer Institute

Neurosurgery

Published

63