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Monitor Tumor pHe and Response Longitudinally during Treatment Using CEST MRI-Detectable Alginate Microbeads

Xiao, Peng, Huang, Jianpan, Han, Xiongqi, Cheu, Jacinth W. S., Liu, Yang, Law, Lok Hin, Lai, Joseph H. C., Li, Jiyu, Park, Se Weon, Wong, Carmen C. L., Lam, Raymond H. W., Chan, Kannie W. Y.·2022·ACS Applied Materials & Interfaces
DOI 10.1021/acsami.2c10493PMC PMC9756293
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Figure 1 Microfluidic fabrication of alginate microbeads incorporated with iopamidol-loaded liposome (Iop-lipobeads). (a) Microfluidic design for the preparation of microbeads. 1, 2, and 3 are inlets for the water phase, oil phase, and oil/acid phase, respectively, and 4 is the outlet. (b) Schematic of Iop-lipobeads. (c) Chemical structure of iopamidol showing exchangeable amide protons generating CEST at 4.2 and 5.6 ppm. (d) Oil phase flow rate dependency of Iop-lipobead size. Iop-lipobead size decreased with the increased flow rate of oil phase when water flow rate and oil/acid flow rate were set at 120 μL/h and 1500 μL/h, respectively. The error bars represent the standard error of the mean. (e) Bright field image of Iop-lipobeads prepared at an oil flow rate of 600 μL/h.
Figure 1 Microfluidic fabrication of alginate microbeads incorporated with iopamidol-loaded liposome (Iop-lipobeads). (a) Microfluidic design for the preparation of microbeads. 1, 2, and 3 are inlets for the water phase, oil phase, and oil/acid phase, respectively, and 4 is the outlet. (b) Schematic of Iop-lipobeads. (c) Chemical structure of iopamidol showing exchangeable amide protons generating CEST at 4.2 and 5.6 ppm. (d) Oil phase flow rate dependency of Iop-lipobead size. Iop-lipobead size decreased with the increased flow rate of oil phase when water flow rate and oil/acid flow rate were set at 120 μL/h and 1500 μL/h, respectively. The error bars represent the standard error of the mean. (e) Bright field image of Iop-lipobeads prepared at an oil flow rate of 600 μL/h.CC BY-NC-ND · PubMed Central
Figure 2 CEST imaging parameter optimization for Iop-lipobeads and stability of CEST contrast over time. (a) Z-spectra and (b) CEST contrast for Iop-lipobeads at B1 values of 0.6, 0.8, 1.2, 1.6, 2.0, and 3.0 μT, and at Tsat = 3 s and 37 °C. (c) B1 power dependency of CEST contrast at 4.2 ppm and −3.4 ppm, showing that CEST contrast at 4.2 ppm reached the highest value at 1.6 and 2.0 μT. (d) Time course of CEST contrast at 4.2 ppm in Iop-lipobeads with daily replacement of saline at 37 °C showed the stability. CEST was measured at 1.6 μT and normalized to day 0. The error bars represent the standard error of the mean.
Figure 2 CEST imaging parameter optimization for Iop-lipobeads and stability of CEST contrast over time. (a) Z-spectra and (b) CEST contrast for Iop-lipobeads at B1 values of 0.6, 0.8, 1.2, 1.6, 2.0, and 3.0 μT, and at Tsat = 3 s and 37 °C. (c) B1 power dependency of CEST contrast at 4.2 ppm and −3.4 ppm, showing that CEST contrast at 4.2 ppm reached the highest value at 1.6 and 2.0 μT. (d) Time course of CEST contrast at 4.2 ppm in Iop-lipobeads with daily replacement of saline at 37 °C showed the stability. CEST was measured at 1.6 μT and normalized to day 0. The error bars represent the standard error of the mean.CC BY-NC-ND · PubMed Central
Figure 3 pH dependency of Iop-lipobeads in a pH range of 6.0 to 8.0. CEST contrast at 4.2 ppm increased with pH and reached the highest value at pH 7.0 at 1.6 μT. (a) Z-spectra and (b) CEST contrast for Iop-lipobeads. (c) pH dependency of CEST contrast at 4.2 ppm and −3.4 ppm. (d) The CEST maps at 4.2 ppm. The error bars represent standard errors.
Figure 3 pH dependency of Iop-lipobeads in a pH range of 6.0 to 8.0. CEST contrast at 4.2 ppm increased with pH and reached the highest value at pH 7.0 at 1.6 μT. (a) Z-spectra and (b) CEST contrast for Iop-lipobeads. (c) pH dependency of CEST contrast at 4.2 ppm and −3.4 ppm. (d) The CEST maps at 4.2 ppm. The error bars represent standard errors.CC BY-NC-ND · PubMed Central
Figure 4 Power optimization for CEST imaging of Iop-lipobeads in mice without a tumor at day 2 (n = 4). (a) Z-spectra and (b) CEST contrast for Iop-lipobeads at B1 of 0.6, 0.8, 1.2, 1.6, and 2.0 μT. (c) B1 power dependency of CEST contrast at 4.2 ppm, showing that CEST contrast at 4.2 ppm reached the highest value at 1.6 μT. (d) Representative CEST map at 4.2 ppm of Iop-lipobeads at different B1 powers. The error bars represent standard errors.
Figure 4 Power optimization for CEST imaging of Iop-lipobeads in mice without a tumor at day 2 (n = 4). (a) Z-spectra and (b) CEST contrast for Iop-lipobeads at B1 of 0.6, 0.8, 1.2, 1.6, and 2.0 μT. (c) B1 power dependency of CEST contrast at 4.2 ppm, showing that CEST contrast at 4.2 ppm reached the highest value at 1.6 μT. (d) Representative CEST map at 4.2 ppm of Iop-lipobeads at different B1 powers. The error bars represent standard errors.CC BY-NC-ND · PubMed Central
Figure 5 CEST maps in mice with or without tumors before treatment, during treatment, and after sodium bicarbonate treatment. (a) Plan for treatment. CEST maps at (b) 4.2 ppm, (c) 3.4 ppm, and (d) −3.4 ppm in a representative mouse with tumor at B1 = 1.6 μT. CEST maps at (e) 4.2 ppm and (f) −3.4 ppm in a representative mouse without tumors.
Figure 5 CEST maps in mice with or without tumors before treatment, during treatment, and after sodium bicarbonate treatment. (a) Plan for treatment. CEST maps at (b) 4.2 ppm, (c) 3.4 ppm, and (d) −3.4 ppm in a representative mouse with tumor at B1 = 1.6 μT. CEST maps at (e) 4.2 ppm and (f) −3.4 ppm in a representative mouse without tumors.CC BY-NC-ND · PubMed Central
Figure 6 CEST contrast change in Iop-lipobeads and tumors in mice before, during, and after sodium bicarbonate treatment. (a) CEST contrast at 4.2 ppm in Iop-lipobeads in mice with tumors (n = 5) and without tumors (n = 4). (b) Amide CEST and NOE contrast in tumors. (c) Relative changes of CEST contrast in Iop-lipobeads in mice with and without tumors and endogenous CEST contrast, i.e., ATP and NOE, which clearly indicated a better pH sensitivity in Iop-lipobeads. The error bars represent standard errors.
Figure 6 CEST contrast change in Iop-lipobeads and tumors in mice before, during, and after sodium bicarbonate treatment. (a) CEST contrast at 4.2 ppm in Iop-lipobeads in mice with tumors (n = 5) and without tumors (n = 4). (b) Amide CEST and NOE contrast in tumors. (c) Relative changes of CEST contrast in Iop-lipobeads in mice with and without tumors and endogenous CEST contrast, i.e., ATP and NOE, which clearly indicated a better pH sensitivity in Iop-lipobeads. The error bars represent standard errors.CC BY-NC-ND · PubMed Central
Figure 7 Hematoxylin and eosin (H&E) staining of subcutaneous Iop-lipobeads 7 days after injection. (a) The center of the Iop-lipobead region and (b) the periphery of the Iop-lipobead region in mice with tumors. (c) The periphery of the Iop-lipobeads region in mice without tumors. Scale bar: 50 μm. Comparison of NOE contrast in the Iop-lipobead regions (core vs periphery) of (d) mice with tumors and (e) mice without tumors. Black arrows and gray arrows indicated the Iop-lipobeads and cells, respectively. The error bars represent standard errors.
Figure 7 Hematoxylin and eosin (H&E) staining of subcutaneous Iop-lipobeads 7 days after injection. (a) The center of the Iop-lipobead region and (b) the periphery of the Iop-lipobead region in mice with tumors. (c) The periphery of the Iop-lipobeads region in mice without tumors. Scale bar: 50 μm. Comparison of NOE contrast in the Iop-lipobead regions (core vs periphery) of (d) mice with tumors and (e) mice without tumors. Black arrows and gray arrows indicated the Iop-lipobeads and cells, respectively. The error bars represent standard errors.CC BY-NC-ND · PubMed Central

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Metadata

Authors
Xiao, P., Huang, J., Han, X., Cheu, J. W. S., Liu, Y., Law, L. H., Lai, J. H. C., Li, J., Park, S. W., Wong, C. C. L., Lam, R. H. W., & Chan, K. W. Y.
Venue
ACS Applied Materials & Interfaces
Publisher
American Chemical Society (ACS)
Published
2022-11-30
Volume
14
Issue
49
Pages
54401-54410
ISSN
  • 1944-8244
  • 1944-8252
DOI
10.1021/acsami.2c10493
PMC
PMC9756293
Cited by
14
References
0
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (unspecified)
Funders
  • Research Grants Council, University Grants Committee (11102218, C1134-20G, PDFS2122-1S01)
  • City University of Hong Kong (7005433, 7005626, 9609307, 9610560, 9667198)
  • National Natural Science Foundation of China (81871409)
  • Hong Kong Centre for Cerebro-cardiovascular Health Engineering
  • Tung Foundation

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CoChat. (2026). Citation check: Monitor Tumor pHe and Response Longitudinally during Treatment Using CEST MRI-Detectable Alginate Microbeads. https://app.cochat.ai/papers/10.1021/acsami.2c10493
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Xiao, P., Huang, J., Han, X., Cheu, J. W. S., Liu, Y., Law, L. H., Lai, J. H. C., Li, J., Park, S. W., Wong, C. C. L., Lam, R. H. W., & Chan, K. W. Y. (2022). Monitor Tumor pHe and Response Longitudinally during Treatment Using CEST MRI-Detectable Alginate Microbeads. ACS Applied Materials & Interfaces. https://doi.org/10.1021/acsami.2c10493