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Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo

Xiang, Xin, Dong, Chuning, Zhou, Lianbo, Liu, Jun, Rabinowitz, Zachary M., Zhang, Yuzhao, Guo, Honghui, He, Feng, Chen, Xingdou, Wang, Yunhua, Cui, Lina, Ma, Xiaowei·2024·Journal of Medicinal Chemistry
DOI 10.1021/acs.jmedchem.4c00179PMC PMC11017977
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Figures

Figure 1 Optimized reaction route to [68Ga]Ga-BGal.
Figure 1 Optimized reaction route to [68Ga]Ga-BGal.CC BY-NC-ND · PubMed Central
Figure 2 Radio-HPLC analysis of [68Ga]Ga-BGal. Top, HPLC analysis of the probe before purification; middle, analysis of the probe after 4 h in serum; bottom, analysis of the probe after purification. The labeling yield was 90.0 ± 4.3%. The radiochemical purity was greater than 95%. The stability of the probe in serum for 4 h was above 95%.
Figure 2 Radio-HPLC analysis of [68Ga]Ga-BGal. Top, HPLC analysis of the probe before purification; middle, analysis of the probe after 4 h in serum; bottom, analysis of the probe after purification. The labeling yield was 90.0 ± 4.3%. The radiochemical purity was greater than 95%. The stability of the probe in serum for 4 h was above 95%.CC BY-NC-ND · PubMed Central
Figure 3 PET images of [68Ga]Ga-BGal incubated with (a) β-Gal, inactive β-Gal, BSA, and PBS, (b) β-Gal for 1, 5, 15, 30, and 60 min, and (c) β-Gal for 0.01, 0.015, 0.022, 0.033, and 0.05 μg/μL and the corresponding quantitative analysis. (Percentage: the band accounts for the entire lane.)
Figure 3 PET images of [68Ga]Ga-BGal incubated with (a) β-Gal, inactive β-Gal, BSA, and PBS, (b) β-Gal for 1, 5, 15, 30, and 60 min, and (c) β-Gal for 0.01, 0.015, 0.022, 0.033, and 0.05 μg/μL and the corresponding quantitative analysis. (Percentage: the band accounts for the entire lane.)CC BY-NC-ND · PubMed Central
Figure 4 PET images of [68Ga]Ga-BGal incubated with (a) the protein extracted from CT26.CL25 and CT26.WT cells, (b) CT26.CL25 for 1, 15, 30, 60, and 120 min, and (c) the protein of CT26.CL25 for 0.009, 0.0375, 0.15, 0.6, and 2.4 μg/μL and the corresponding quantitative analysis. (Percentage: the band accounts for the entire lane.)
Figure 4 PET images of [68Ga]Ga-BGal incubated with (a) the protein extracted from CT26.CL25 and CT26.WT cells, (b) CT26.CL25 for 1, 15, 30, 60, and 120 min, and (c) the protein of CT26.CL25 for 0.009, 0.0375, 0.15, 0.6, and 2.4 μg/μL and the corresponding quantitative analysis. (Percentage: the band accounts for the entire lane.)CC BY-NC-ND · PubMed Central
Figure 5 Binding modes of [68Ga]Ga-BGal with (a) E. coli β-Gal and (b) human β-Gal.
Figure 5 Binding modes of [68Ga]Ga-BGal with (a) E. coli β-Gal and (b) human β-Gal.CC BY-NC-ND · PubMed Central
Figure 6 Uptake of [68Ga]Ga-BGal in CT26.CL25, CT26.WT, saline-treated HeLa, and DOX-treated HeLa cells. (a) Dynamic uptake of the probe in CT26.CL25 and CT26.WT cells with or without β-Gal at 0.5, 1, 2, and 4 h. (b) Dynamic uptake of the probe in saline-treated HeLa and DOX-treated HeLa cells at 0.5, 1, 2, and 4 h. (c) Quantitative analysis of the probe in CT26.CL25, CT26.WT, saline-treated HeLa, and DOX-treated HeLa cells at 4 h incubation. (d) Uptake of the probe in CT26.CL25 and CT26.WT with different quantities (0.125, 0.25, 0.5, and 1 μg) of β-Gal after 4 h of incubation (*p < 0.05, **p < 0.01, ***p < 0.001).
Figure 6 Uptake of [68Ga]Ga-BGal in CT26.CL25, CT26.WT, saline-treated HeLa, and DOX-treated HeLa cells. (a) Dynamic uptake of the probe in CT26.CL25 and CT26.WT cells with or without β-Gal at 0.5, 1, 2, and 4 h. (b) Dynamic uptake of the probe in saline-treated HeLa and DOX-treated HeLa cells at 0.5, 1, 2, and 4 h. (c) Quantitative analysis of the probe in CT26.CL25, CT26.WT, saline-treated HeLa, and DOX-treated HeLa cells at 4 h incubation. (d) Uptake of the probe in CT26.CL25 and CT26.WT with different quantities (0.125, 0.25, 0.5, and 1 μg) of β-Gal after 4 h of incubation (*p < 0.05, **p < 0.01, ***p < 0.001).CC BY-NC-ND · PubMed Central
Figure 7 (a, b) Representative PET images obtained at 10 min, 30 min, 1, 2, and 4 h after injection of [68Ga]Ga-BGal in (a) CT26.WT and (b) CT26.CL25 tumor-bearing mice (the red circle represents the tumors). (c) Quantitative analysis of the probe in the heart, liver, kidneys, tumor, muscle, and tumor/muscle ratio from (a, b). (d) Biodistribution of the probe in CT26.WT and CT26.CL25 tumor-bearing mice at 4 h after injection and analysis of the tumor-to-muscle ratio (**p < 0.01, ***p < 0.001).
Figure 7 (a, b) Representative PET images obtained at 10 min, 30 min, 1, 2, and 4 h after injection of [68Ga]Ga-BGal in (a) CT26.WT and (b) CT26.CL25 tumor-bearing mice (the red circle represents the tumors). (c) Quantitative analysis of the probe in the heart, liver, kidneys, tumor, muscle, and tumor/muscle ratio from (a, b). (d) Biodistribution of the probe in CT26.WT and CT26.CL25 tumor-bearing mice at 4 h after injection and analysis of the tumor-to-muscle ratio (**p < 0.01, ***p < 0.001).CC BY-NC-ND · PubMed Central
Figure 8 (a, b) Representative PET images obtained at 10 min, 30 min, 1, 2, and 4 h after injection of [68Ga]Ga-BGal in (a) saline-treated HeLa and (b) DOX-treated HeLa tumor-bearing mice (the red circle represents the tumors). (c) Quantitative analysis of the probe in the heart, liver, kidneys, tumor, muscle, and tumor/muscle ratio from (a, b). (d) Biodistribution of the probe in saline-treated HeLa and DOX-treated HeLa tumor-bearing mice at 4 h after injection and analysis of the tumor-to-muscle ratio (*p < 0.05, **p < 0.01).
Figure 8 (a, b) Representative PET images obtained at 10 min, 30 min, 1, 2, and 4 h after injection of [68Ga]Ga-BGal in (a) saline-treated HeLa and (b) DOX-treated HeLa tumor-bearing mice (the red circle represents the tumors). (c) Quantitative analysis of the probe in the heart, liver, kidneys, tumor, muscle, and tumor/muscle ratio from (a, b). (d) Biodistribution of the probe in saline-treated HeLa and DOX-treated HeLa tumor-bearing mice at 4 h after injection and analysis of the tumor-to-muscle ratio (*p < 0.05, **p < 0.01).CC BY-NC-ND · PubMed Central

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Metadata

Authors
Xiang, X., Dong, C., Zhou, L., Liu, J., Rabinowitz, Z. M., Zhang, Y., Guo, H., He, F., Chen, X., Wang, Y., Cui, L., & Ma, X.
Venue
Journal of Medicinal Chemistry
Publisher
American Chemical Society (ACS)
Published
2024-03-20
Volume
67
Issue
7
Pages
5924-5934
ISSN
  • 0022-2623
  • 1520-4804
DOI
10.1021/acs.jmedchem.4c00179
PMC
PMC11017977
Cited by
41
References
10
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 365 d)
Funders
  • Fundamental Research Funds for Central Universities of the Central South University (2022ZZTS0856)
  • National Institute on Aging (R41AG081007)
  • Key Research and Development Program of Hunan Province of China (2022SK2035)

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