Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor
Abstract
:1. Introduction
2. Results
2.1. Preparation and Characterization of DFO-Anti-PD-L1-mAb Conjugates
2.2. Radiolabeling and In Vitro Stability Study
2.3. 89Zr-iPET Imaging
2.4. Biodistribution and Pharmacokinetics
2.5. Pathological Examination and IHC
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Preparation and Characterization of DFO-Anti-PD-L1-mAb Conjugates
4.3. Radiolabeling and In Vitro Stability Study
4.4. Cell Culture and Animal Model Establishment
4.5. Animal Positron Emission Tomography Imaging
4.6. Biodistribution and Pharmacokinetics
4.7. Pathological and Immunohistochemistry Examinations
4.8. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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DFO-Anti-PD-L1-mAb Conjugate | Reaction Condition | Quality Control | ||||||
---|---|---|---|---|---|---|---|---|
Temp. (°C) | pH | Reaction Time (min) | Molar Excess of DFO to Antibody (Fold) | Visual Inspection | pH | Chemical Yield (%) | Chelator-to-Antibody Ratio (Avg. CAR) | |
DFO-mAb conjugate_3X | 25 | 9.0 | 50 | 3 | transparent | 7.0–7.5 | 100 | 0.4 |
DFO-mAb conjugate_10X | 25 | 9.0 | 50 | 10 | transparent | 7.0–7.5 | 100 | 1.4 |
DFO-mAb conjugate_20X | 25 | 9.0 | 50 | 20 | transparent | 7.0–7.5 | 100 | 2.0 |
Subject | 89Zr-DFO-Anti-PD-L1-mAb Tracers | ||
---|---|---|---|
Tracer_3X | Tracer_10X | Tracer_20X | |
Visual inspection | Transparent | Transparent | Transparent |
Radiochemical yield (%) | 24.3 ± 7.1 | 91.1 ± 3.2 | 98.7 ± 0.5 |
Radiochemical purity (%) | 99.0 ± 0.8 | 100.0 ± 0.0 | 100.0 ± 0.0 |
Specific activity at the end of synthesis (μCi/μg) | 2.2 ± 0.6 | 8.2 ± 0.6 | 10.5 ± 1.6 |
Protein dose injected for imaging study (μg) | 8–10 | 8–10 | 8–10 |
Parameter | Unit | Value of 89Zr-DFO-Anti-PD-L1-mAb Tracers | ||
---|---|---|---|---|
Tracer_3X | Tracer_10X | Tracer_20X | ||
Cmax | %ID/g | 42.0 ± 3.5 | 44.2 ± 3.3 | 51.9 ± 0.9 |
Tmax | h | 0.083 | 0.083 | 0.083 |
Cl | g/h | 0.22 ± 0.03 | 0.26 ± 0.02 | 0.20 ± 0.01 |
MRT | h | 25.4 ± 4.9 | 24.2 ± 6.1 | 25.8 ± 3.3 |
T1/2 | h | 11.8 ± 0.5 | 11.1 ± 0.7 | 11.7 ± 0.6 |
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Tsai, S.-C.; Farn, S.-S.; Lo, W.-L.; Ou Yang, F.-Y.; Kang, Y.-C.; Chen, L.-C.; Chen, K.-T.; Liao, J.-W.; Kung, J.-Y.; Chen, J.-T.; et al. Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor. Int. J. Mol. Sci. 2023, 24, 17132. https://doi.org/10.3390/ijms242417132
Tsai S-C, Farn S-S, Lo W-L, Ou Yang F-Y, Kang Y-C, Chen L-C, Chen K-T, Liao J-W, Kung J-Y, Chen J-T, et al. Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor. International Journal of Molecular Sciences. 2023; 24(24):17132. https://doi.org/10.3390/ijms242417132
Chicago/Turabian StyleTsai, Shih-Chuan, Shiou-Shiow Farn, Wei-Lin Lo, Fang-Yu Ou Yang, Yong-Ching Kang, Liang-Cheng Chen, Kuo-Ting Chen, Jiunn-Wang Liao, Jui-Yin Kung, Jenn-Tzong Chen, and et al. 2023. "Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor" International Journal of Molecular Sciences 24, no. 24: 17132. https://doi.org/10.3390/ijms242417132