Image-guided surgery of head and neck carcinoma in rabbit models by intra-operatively defining tumour-infiltrated margins and metastatic lymph nodes

Pengpeng Sun; Yunfei Zhang; Kaicheng Li; Cong Wang; Feng Zeng; Jinyu Zhu; Yingwei Wu; Xiaofeng Tao

doi:10.1016/j.ebiom.2019.10.055

Image-guided surgery of head and neck carcinoma in rabbit models by intra-operatively defining tumour-infiltrated margins and metastatic lymph nodes

EBioMedicine. 2019 Dec:50:93-102. doi: 10.1016/j.ebiom.2019.10.055. Epub 2019 Nov 13.

Authors

Pengpeng Sun¹, Yunfei Zhang², Kaicheng Li³, Cong Wang⁴, Feng Zeng⁵, Jinyu Zhu⁶, Yingwei Wu⁷, Xiaofeng Tao⁸

Affiliations

¹ Department of Radiology, School of Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, 639 Zhizao Ju Road, Shanghai 200011, China.
² School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai 201203, China; United Imaging Healthcare, Shanghai, 201807, China.
³ Department of Radiology, School of Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, 639 Zhizao Ju Road, Shanghai 200011, China; Department of Radiology, Hainan West Central Hospital, Dan Zhou, Hai Nan, 571700, China.
⁴ School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai 201203, China.
⁵ School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai 201203, China; Pi-Wei Institute, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
⁶ Department of Radiology, School of Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, 639 Zhizao Ju Road, Shanghai 200011, China; Department of Radiology, Shanghai Six People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
⁷ Department of Radiology, School of Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, 639 Zhizao Ju Road, Shanghai 200011, China. Electronic address: [email protected].
⁸ Department of Radiology, School of Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, 639 Zhizao Ju Road, Shanghai 200011, China. Electronic address: [email protected].

Abstract

Background: The infiltrative nature and lymphatic metastasis of head and neck squamous cell carcinoma (HNSCC) are the main reasons leading to its poor prognosis.

Methods: A multimodal surface-enhanced resonance Raman spectroscopy (SERRS) and magnetic resonance (MR) nanoprobe, in which paramagnetic chelators and heptamethine cyanine-based Raman reporter molecules were functionalized on a gold nanostar (AuS) surface was developed. Preoperative MRI and intraoperative SERRS-guided surgery were performed on rabbits bearing head and neck VX2 tumours to determine feasibility of the MR/SERRS probe in defining tumour marginal infiltration and lymph nodes metastasis.

Findings: Preoperative T1-weighted MRI (T1W-MRI) unambiguously delineated the orthotopic head and neck VX2 tumour xenograft and detected the metastatic lymph nodes in rabbit models after intravenous administration of the probe. With the assistance of a hand-held Raman detector, the probe not only intra-operatively demarcated invasive tumour margins but also successfully distinguished metastatic lymph nodes via a remarkable attenuated Raman signal. Importantly, the group of rabbits subjected to the SERRS-guided surgery exhibited prolonged median survival time (78 days) compared with that of the control group without surgical intervention (29 days) or the group treated with conventional white-light-guided surgery (42 days) (P < 0.0001).

Interpretation: we developed a novel AuS-based multimodal MR/SERRS probe. The capability of this probe to identify both a tumour xenograft and metastatic lymph nodes preoperatively by MRI and intra-operatively by SERRS not only avoids the need for unnecessary resection of neurological structures but also provides a new opportunity to improve the surgical prognosis of head and neck carcinoma of infiltrative nature.

Keywords: Head and neck squamous cell carcinoma (HNSCC); Image-guided resection; Lymph node metastasis; Magnetic resonance imaging (MRI); Surface-enhanced resonance Raman scattering (SERRS).

MeSH terms

Animals
Carcinoma / diagnosis*
Carcinoma / mortality
Carcinoma / surgery*
Cell Line, Tumor
Disease Models, Animal
Head and Neck Neoplasms / diagnosis*
Head and Neck Neoplasms / mortality
Head and Neck Neoplasms / surgery*
Humans
Lymphatic Metastasis
Magnetic Resonance Imaging
Margins of Excision
Molecular Probes / chemical synthesis
Molecular Probes / chemistry
Neoplasm Invasiveness
Neoplasm Staging
Rabbits
Spectrum Analysis, Raman
Surgery, Computer-Assisted* / methods
Treatment Outcome

Substances

Molecular Probes