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Theranostics 2024; 14(2):819-829. doi:10.7150/thno.91554 This issue Cite

Research Paper

Lower-grade gliomas surgery guided by GRPR-targeting PET/NIR dual-modality image probe: a prospective and single-arm clinical trial

Liangpeng Chen, MD^1*, Jingjing Zhang, MD^2,3,4*, Chongwei Chi, PhD^5*, Wenqiang Che, MD¹, Gehong Dong, MD⁶, Junmei Wang, MD⁷, Yanru Du, MD⁶, Rongxi Wang, MD⁸, Zhaohui Zhu, MD⁸, Jie Tian, PhD^5✉, Nan Ji, MD^1,9✉, Xiaoyuan Chen, PhD^2,3,4✉, Deling Li, MD^1,9✉

1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
2. Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore.
3. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
4. Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5. Key Laboratory of Molecular Imaging, Chinese Academy of Science, Beijing, China.
6. Department of Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
7. Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
8. Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
9. China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, China.
* First author.

✉ Corresponding authors: Deling Li; Affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Key Laboratory of Molecular Imaging, Chinese Academy of Science, Beijing, China; China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, China; Postal/mail address: No.119 South Fourth Ring West Road, Beijing,100070, China; E-mail: lidelingorg; Tel.: 010-59976512. Xiaoyuan Chen; Affiliation: Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore; Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Postal/mail address: 1E Kent Ridge Road, 119228, Singapore; E-mail: chen.shawnedu.sg; Tel.: +65 6772 4211. Nan Ji; Affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, China; Postal/mail address: No.119 South Fourth Ring West Road, Beijing,100070, China; E-mail: jinanorg; Tel.: 010-59978402. Jie Tian; Affiliation: Key Laboratory of Molecular Imaging, Chinese Academy of Science, Beijing, China; Postal/mail address: Flr 9, Bldg Zhinenghua, No 95, Zhongguancun East Rd, Haidian District, 100190, Beijing; E-mail: jie.tianac.cn; Tel.: 010-82618465. More

Abstract

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 (NCT 03407781) 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.

Keywords: Lower-grade gliomas, Dual-modality imaging, Positron emission tomography, Near-infrared fluorescence, Intraoperative imaging, Gastrin-releasing peptide receptor

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