Dataset Information

Image-guided surgery with a new tumour-targeting probe improves the identification of positive margins.

ABSTRACT:

Background

Given the lack of visual discrepancy between malignant and surrounding normal tissue, current breast conserving surgery (BCS) is associated with a high re-excision rate. Due to the increasing cases of BCS, a novel method of complete tumour removal at the initial surgical resection is critically needed in the operating room to help optimize the surgical procedure and to confirm tumour-free edges.

Methods

We developed a unique near-infrared (NIR) fluorescence imaging probe, ICG-p28, composed of the clinically nontoxic tumour-targeting peptide p28 and the FDA-approved NIR dye indocyanine green (ICG). ICG-p28 was characterized in vitro and evaluated in multiple breast cancer animal models with appropriate control probes. Our experimental approach with multiple-validations and -blinded procedures was designed to determine whether ICG-p28 can accurately identify tumour margins in mimicked intraoperative settings.

Findings

The in vivo kinetics were analysed to optimize settings for potential clinical use. Xenograft tumours stably expressing iRFP as a tumour marker showed significant colocalization with ICG-p28, but not ICG alone. Image-guided surgery with ICG-p28 showed an over 6.6 × 10³-fold reduction in residual normalized tumour DNA at the margin site relative to control approaches (i.e., surgery with ICG or palpation/visible inspection alone), resulting in an improved tumour recurrence rate (92% specificity) in multiple breast cancer animal models independent of the receptor expression status. ICG-p28 allowed accurate identification of tumour cells in the margin to increase the complete resection rate.

Interpretation

Our simple and cost-effective approach has translational potential and offers a new surgical procedure that enables surgeons to intraoperatively identify tumour margins in a real-time, 3D fashion and that notably improves overall outcomes by reducing re-excision rates.

Funding

This work was supported by NIH/ National Institute of Biomedical Imaging and Bioengineering, R01EB023924.

SUBMITTER: Goto M

PROVIDER: S-EPMC8814381 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Image-guided surgery with a new tumour-targeting probe improves the identification of positive margins.

Goto Masahide M Ryoo Ingeun I Naffouje Samer S Mander Sunam S Christov Konstantin K Wang Jing J Green Albert A Shilkaitis Anne A Das Gupta Tapas K TK Yamada Tohru T

EBioMedicine 20220130

<h4>Background</h4>Given the lack of visual discrepancy between malignant and surrounding normal tissue, current breast conserving surgery (BCS) is associated with a high re-excision rate. Due to the increasing cases of BCS, a novel method of complete tumour removal at the initial surgical resection is critically needed in the operating room to help optimize the surgical procedure and to confirm tumour-free edges.<h4>Methods</h4>We developed a unique near-infrared (NIR) fluorescence imaging prob ...[more]

PMID: 35108666

Similar Datasets

Project description:Complete tumor removal during surgery has a great impact on patient survival. To that end, the surgeon should detect the tumor, remove it and validate that there are no residual cancer cells left behind. Residual cells at the incision margin of the tissue removed during surgery are associated with tumor recurrence and poor prognosis for the patient. In order to remove the tumor tissue completely with minimal collateral damage to healthy tissue, there is a need for diagnostic tools that will differentiate between the tumor and its normal surroundings. Methods: We designed, synthesized and characterized three novel polymeric Turn-ON probes that will be activated at the tumor site by cysteine cathepsins that are highly expressed in multiple tumor types. Utilizing orthotopic breast cancer and melanoma models, which spontaneously metastasize to the brain, we studied the kinetics of our polymeric Turn-ON nano-probes. Results: To date, numerous low molecular weight cathepsin-sensitive substrates have been reported, however, most of them suffer from rapid clearance and reduced signal shortly after administration. Here, we show an improved tumor-to-background ratio upon activation of our Turn-ON probes by cathepsins. The signal obtained from the tumor was stable and delineated the tumor boundaries during the whole surgical procedure, enabling accurate resection. Conclusions: Our findings show that the control groups of tumor-bearing mice, which underwent either standard surgery under white light only or under the fluorescence guidance of the commercially-available imaging agents ProSense® 680 or 5-aminolevulinic acid (5-ALA), survived for less time and suffered from tumor recurrence earlier than the group that underwent image-guided surgery (IGS) using our Turn-ON probes. Our "smart" polymeric probes can potentially assist surgeons' decision in real-time during surgery regarding the tumor margins needed to be removed, leading to improved patient outcome.

Project description:Purpose: Lower-grade gliomas (LGGs) are a group of infiltrative growing glial brain tumors characterized by intricate intratumoral heterogeneity and subtle visual appearance differences from non-tumor tissue, which can lead to errors in pathologic tissue sampling. Although 5-ALA fluorescence has been an essential method for visualizing gliomas during surgery, its effectiveness is limited in the case of LGGs due to low sensitivity. Therefore, we developed a novel PET/NIR dual-modality image probe targeting gastrin-releasing peptide receptor (GRPR) in glioma cells to enhance tumor visualization and improve the accuracy of sampling. Methods: A prospective, non-randomized, single-center feasibility clinical trial (NCT03407781) was conducted in the referral center from October 21, 2016, to August 17, 2018. Consecutive enrollment included patients suspected of having LGGs and considered suitable candidates for surgical removal. Group 1 comprised ten patients who underwent preoperative 68Ga-IRDye800CW-BBN PET/MRI assessment followed by intraoperative fluorescence-guided surgery. Group 2 included 42 patients who underwent IRDye800CW-BBN fluorescence-guided surgery. The primary endpoints were the predictive value of preoperative PET imaging for intraoperative fluorescence and the sensitivity and specificity of fluorescence-guided sampling. Results: Thirty-nine patients were included in the in-depth analysis of endpoints, with 25 (64.1%) exhibiting visible fluorescence, while 14 (35.9%) did not. The preoperative positive PET uptake exhibited a greater accuracy in predicting intraoperative fluorescence compared to MRI enhancement (100% [10/10] vs. 87.2% [34/39]). A total of 125 samples were harvested during surgery. Compared with pathology, subjective fluorescence intensity showed a sensitivity of 88.6% and a specificity of 88.2% in identifying WHO grade III samples. For WHO grade II samples, the sensitivity and specificity of fluorescence were 54.7% and 88.2%, respectively. Conclusion: This study has demonstrated the feasibility of the novel dual-modality imaging technique for integrated pre- and intraoperative targeted imaging via the same molecular receptor in surgeries for LGGs. The PET/NIR dual-modality probe exhibits promise for preoperative surgical planning in fluorescence-guided surgery and provides greater accuracy in guiding tumor sampling compared to 5-ALA in patients with LGGs.

Dataset Information

Image-guided surgery with a new tumour-targeting probe improves the identification of positive margins.

Background

Methods

Findings

Interpretation

Funding

Publications

Image-guided surgery with a new tumour-targeting probe improves the identification of positive margins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets