89Zr-Labeled Domain II-Specific scFv-Fc ImmunoPET Probe for Imaging Epidermal Growth Factor Receptor In Vivo
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Characterization of Antibody
2.2. Cell Lines and Xenografts
2.3. Conjugation of Antibodies with Bifunctional Chelators
2.4. Production and Characterization of 89Zr-Oxalate
2.5. Radiolabeling and Characterization of 89Zr-8709-scFv-Fc and 111In-Nimotuzumab
2.6. In Vitro Binding
2.7. Biodistribution and Pharmacokinetics
2.8. EGFR Domain Specific Imaging Using 111In-Nimotuzumab and 89Zr-8709-scFv-Fc
2.9. Statistical Analysis
2.10. Data Availability
3. Results
3.1. Conjugation and Quality Control of Immunoconjugates
3.2. Radiolabeling of 89Zr-DFO-8709 ScFv-Fc and 111In-Nimotuzumab
3.3. In Vitro Binding
3.4. Biodistribution and Pharmacokinetics
3.5. MicroPET/SPECT/CT Imaging Using 111In-Nimotuzumab and 89Zr-8709-scFv-Fc
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
EGFR | Epidermal Growth Factor Receptor |
PET | Positron Emission Tomography |
SPECT | Single Photon Emission Computed Tomography |
CT | Computed Tomography |
89Zr | Zirconium-89 |
111In | Indium-111 |
DFO | Deferoxamine |
HPLC | High Pressure Liquid Chromatography |
SEC-HPLC | Size Exclusion HPLC |
iTLC | Instant Thin Layer Chromatography |
BLI | Biolayer interferometry |
KD | Binding Constant |
%IA/g | % Injected Activity per Gram |
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Compound | t1/2α (h) | t1/2β (h) | AUC (% IA.h/mL) | V1 (mL) | CL (mL/h) |
---|---|---|---|---|---|
89Zr-8709-scFv-Fc | 1.5 ± 1.2 | 119.2 ± 1.3 | 846.5 ± 12.9 | 13.6 ± 0.5 | 5.6 ± 0.3 |
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Alizadeh, E.; Behlol Ayaz Ahmed, K.; Raja Solomon, V.; Gaja, V.; Bernhard, W.; Makhlouf, A.; Gonzalez, C.; Barreto, K.; Casaco, A.; Geyer, C.R.; et al. 89Zr-Labeled Domain II-Specific scFv-Fc ImmunoPET Probe for Imaging Epidermal Growth Factor Receptor In Vivo. Cancers 2021, 13, 560. https://doi.org/10.3390/cancers13030560
Alizadeh E, Behlol Ayaz Ahmed K, Raja Solomon V, Gaja V, Bernhard W, Makhlouf A, Gonzalez C, Barreto K, Casaco A, Geyer CR, et al. 89Zr-Labeled Domain II-Specific scFv-Fc ImmunoPET Probe for Imaging Epidermal Growth Factor Receptor In Vivo. Cancers. 2021; 13(3):560. https://doi.org/10.3390/cancers13030560
Chicago/Turabian StyleAlizadeh, Elahe, Khan Behlol Ayaz Ahmed, Viswas Raja Solomon, Vijay Gaja, Wendy Bernhard, Amal Makhlouf, Carolina Gonzalez, Kris Barreto, Angel Casaco, C. Ronald Geyer, and et al. 2021. "89Zr-Labeled Domain II-Specific scFv-Fc ImmunoPET Probe for Imaging Epidermal Growth Factor Receptor In Vivo" Cancers 13, no. 3: 560. https://doi.org/10.3390/cancers13030560
APA StyleAlizadeh, E., Behlol Ayaz Ahmed, K., Raja Solomon, V., Gaja, V., Bernhard, W., Makhlouf, A., Gonzalez, C., Barreto, K., Casaco, A., Geyer, C. R., & Fonge, H. (2021). 89Zr-Labeled Domain II-Specific scFv-Fc ImmunoPET Probe for Imaging Epidermal Growth Factor Receptor In Vivo. Cancers, 13(3), 560. https://doi.org/10.3390/cancers13030560