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Author Spotlight: Multimodal Imaging Strategies for Optimizing Drug Delivery and Early Detection in Glioblastoma Treatment
Published on: March 1, 2024
Near-infrared II fluorescence-guided glioblastoma surgery targeting monocarboxylate transporter 4 combined with
Hongyang Zhao1, Chunzhao Li2, Xiaojing Shi3
1Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China; CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China; Jilin Province Neuro-oncology Engineering Laboratory, Changchun, China; Jilin Provincial Key Laboratory of Neuro-oncology, Changchun, China.
Background:
Surgery is crucial for glioma treatment, but achieving complete tumour removal remains challenging. We evaluated the effectiveness of a probe targeting monocarboxylate transporter 4 (MCT4) in recognising gliomas, and of near-infrared window II (NIR-II) fluorescent molecular imaging and photothermal therapy as treatment strategies.
Methods:
We combined an MCT4-specific monoclonal antibody with indocyanine green to create the probe. An orthotopic mouse model and a transwell model were used to evaluate its ability to guide tumour resection using NIR-II fluorescence and to penetrate the blood-brain barrier (BBB), respectively. A subcutaneous tumour model was established to confirm photothermal therapy efficacy. Probe specificity was assessed in brain tissue from mice and humans. Finally, probe effectiveness in photothermal therapy was investigated.
Findings:
MCT4 was differentially expressed in tumour and normal brain tissue. The designed probe exhibited precise tumour targeting. Tumour imaging was precise, with a signal-to-background (SBR) ratio of 2.8. Residual tumour cells were absent from brain tissue postoperatively (SBR: 6.3). The probe exhibited robust penetration of the BBB. Moreover, the probe increased the tumour temperature to 50 °C within 5 min of laser excitation. Photothermal therapy significantly reduced tumour volume and extended survival time in mice without damage to vital organs.
Interpretation:
These findings highlight the potential efficacy of our probe for fluorescence-guided surgery and therapeutic interventions.
Funding:
Jilin Province Department of Science and Technology (20200403079SF), Department of Finance (2021SCZ06) and Development and Reform Commission (20200601002JC); National Natural Science Foundation of China (92059207, 92359301, 62027901, 81930053, 81227901, U21A20386); and CAS Youth Interdisciplinary Team (JCTD-2021-08).
Insights
A novel probe targeting monocarboxylate transporter 4 (MCT4) enables precise glioma detection using near-infrared window II (NIR-II) fluorescence imaging. This probe also facilitates effective photothermal therapy, improving surgical outcomes and survival rates in preclinical models.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Oncology
Background:
- Glioma surgery faces challenges in achieving complete tumor removal.
- Monocarboxylate transporter 4 (MCT4) is a potential biomarker for glioma detection.
- Near-infrared window II (NIR-II) fluorescence imaging offers deep tissue penetration for biomedical applications.
Purpose of the Study:
- To develop and evaluate a novel probe for MCT4-targeted glioma detection.
- To assess the probe's efficacy in fluorescence-guided surgery using NIR-II imaging.
- To investigate the probe's potential for photothermal therapy in glioma treatment.
Main Methods:
- An MCT4-specific monoclonal antibody was conjugated with indocyanine green to create the probe.
- Probe performance was evaluated in orthotopic and subcutaneous mouse models, and a transwell model for blood-brain barrier (BBB) penetration.
- Tumor targeting, NIR-II fluorescence imaging, and photothermal therapy efficacy were assessed in vivo and in vitro.
Main Results:
- The probe demonstrated specific and precise targeting of gliomas with high signal-to-background ratios (SBR) for both imaging (2.8) and postsurgical assessment (6.3).
- The probe successfully penetrated the blood-brain barrier (BBB) and enabled effective photothermal therapy, increasing tumor temperature to 50°C within 5 minutes.
- Photothermal therapy significantly reduced tumor volume and prolonged survival in mice without causing damage to vital organs.
Conclusions:
- The developed MCT4-targeting probe shows significant potential for improving fluorescence-guided surgery in gliomas.
- This probe offers a dual-modality approach for both diagnostic imaging and therapeutic intervention in glioma treatment.
- Further research is warranted to translate this promising technology into clinical practice.
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