Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment
Treating glioblastoma and monitoring treatment response non-invasively remain challenging. Here, we developed a robust approach using a drug-loaded liposomal hydrogel that is mechanically compatible with the brain, and, simultaneously, we successfully monitored early tumor response using Chemical Ex...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-01-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/16/1/101 |
| _version_ | 1797342709084585984 |
|---|---|
| author | Se-Weon Park Joseph H. C. Lai Xiongqi Han Vivian W. M. Leung Peng Xiao Jianpan Huang Kannie W. Y. Chan |
| author_facet | Se-Weon Park Joseph H. C. Lai Xiongqi Han Vivian W. M. Leung Peng Xiao Jianpan Huang Kannie W. Y. Chan |
| author_sort | Se-Weon Park |
| collection | DOAJ |
| description | Treating glioblastoma and monitoring treatment response non-invasively remain challenging. Here, we developed a robust approach using a drug-loaded liposomal hydrogel that is mechanically compatible with the brain, and, simultaneously, we successfully monitored early tumor response using Chemical Exchange Saturation Transfer (CEST) MRI. This CEST-detectable liposomal hydrogel was optimized based on a sustainable drug release and a soft hydrogel for the brain tumor, which is unfavorable for tumor cell proliferation. After injecting the hydrogel next to the tumor, three distinctive CEST contrasts enabled the monitoring of tumor response and drug release longitudinally at 3T. As a result, a continuous tumor volume decrease was observed in the treatment group along with a significant decrease in CEST contrasts relating to the tumor response at 3.5 ppm (Amide Proton Transfer; APT) and at −3.5 ppm (relayed Nuclear Overhauser Effect; rNOE) when compared to the control group (<i>p</i> < 0.05). Interestingly, the molecular change at 3.5 ppm on day 3 (<i>p</i> < 0.05) was found to be prior to the significant decrease in tumor volume on day 5. An APT signal also showed a strong correlation with the number of proliferating cells in the tumors. This demonstrated that APT detected a distinctive decrease in mobile proteins and peptides in tumors before the change in tumor morphology. Moreover, the APT signal showed a regional response to the treatment, associated with proliferating and apoptotic cells, which allowed an in-depth evaluation and prediction of the tumor treatment response. This newly developed liposomal hydrogel allows image-guided brain tumor treatment to address clinical needs using CEST MRI. |
| first_indexed | 2024-03-08T10:37:13Z |
| format | Article |
| id | doaj.art-2e7832c1b6b1453aaca3fffeeccd41ab |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-08T10:37:13Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2e7832c1b6b1453aaca3fffeeccd41ab2024-01-26T18:07:35ZengMDPI AGPharmaceutics1999-49232024-01-0116110110.3390/pharmaceutics16010101Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor TreatmentSe-Weon Park0Joseph H. C. Lai1Xiongqi Han2Vivian W. M. Leung3Peng Xiao4Jianpan Huang5Kannie W. Y. Chan6Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, ChinaDepartment of Biomedical Engineering, City University of Hong Kong, Hong Kong, ChinaDepartment of Biomedical Engineering, City University of Hong Kong, Hong Kong, ChinaDepartment of Biomedical Engineering, City University of Hong Kong, Hong Kong, ChinaDepartment of Biomedical Engineering, City University of Hong Kong, Hong Kong, ChinaDepartment of Diagnostic Radiology, The University of Hong Kong, Hong Kong, ChinaDepartment of Biomedical Engineering, City University of Hong Kong, Hong Kong, ChinaTreating glioblastoma and monitoring treatment response non-invasively remain challenging. Here, we developed a robust approach using a drug-loaded liposomal hydrogel that is mechanically compatible with the brain, and, simultaneously, we successfully monitored early tumor response using Chemical Exchange Saturation Transfer (CEST) MRI. This CEST-detectable liposomal hydrogel was optimized based on a sustainable drug release and a soft hydrogel for the brain tumor, which is unfavorable for tumor cell proliferation. After injecting the hydrogel next to the tumor, three distinctive CEST contrasts enabled the monitoring of tumor response and drug release longitudinally at 3T. As a result, a continuous tumor volume decrease was observed in the treatment group along with a significant decrease in CEST contrasts relating to the tumor response at 3.5 ppm (Amide Proton Transfer; APT) and at −3.5 ppm (relayed Nuclear Overhauser Effect; rNOE) when compared to the control group (<i>p</i> < 0.05). Interestingly, the molecular change at 3.5 ppm on day 3 (<i>p</i> < 0.05) was found to be prior to the significant decrease in tumor volume on day 5. An APT signal also showed a strong correlation with the number of proliferating cells in the tumors. This demonstrated that APT detected a distinctive decrease in mobile proteins and peptides in tumors before the change in tumor morphology. Moreover, the APT signal showed a regional response to the treatment, associated with proliferating and apoptotic cells, which allowed an in-depth evaluation and prediction of the tumor treatment response. This newly developed liposomal hydrogel allows image-guided brain tumor treatment to address clinical needs using CEST MRI.https://www.mdpi.com/1999-4923/16/1/101glioblastomaCEST MRIliposomehydrogeltreatment |
| spellingShingle | Se-Weon Park Joseph H. C. Lai Xiongqi Han Vivian W. M. Leung Peng Xiao Jianpan Huang Kannie W. Y. Chan Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment Pharmaceutics glioblastoma CEST MRI liposome hydrogel treatment |
| title | Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment |
| title_full | Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment |
| title_fullStr | Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment |
| title_full_unstemmed | Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment |
| title_short | Preclinical Application of CEST MRI to Detect Early and Regional Tumor Response to Local Brain Tumor Treatment |
| title_sort | preclinical application of cest mri to detect early and regional tumor response to local brain tumor treatment |
| topic | glioblastoma CEST MRI liposome hydrogel treatment |
| url | https://www.mdpi.com/1999-4923/16/1/101 |
| work_keys_str_mv | AT seweonpark preclinicalapplicationofcestmritodetectearlyandregionaltumorresponsetolocalbraintumortreatment AT josephhclai preclinicalapplicationofcestmritodetectearlyandregionaltumorresponsetolocalbraintumortreatment AT xiongqihan preclinicalapplicationofcestmritodetectearlyandregionaltumorresponsetolocalbraintumortreatment AT vivianwmleung preclinicalapplicationofcestmritodetectearlyandregionaltumorresponsetolocalbraintumortreatment AT pengxiao preclinicalapplicationofcestmritodetectearlyandregionaltumorresponsetolocalbraintumortreatment AT jianpanhuang preclinicalapplicationofcestmritodetectearlyandregionaltumorresponsetolocalbraintumortreatment AT kanniewychan preclinicalapplicationofcestmritodetectearlyandregionaltumorresponsetolocalbraintumortreatment |