HER3 PET Imaging: 68Ga-Labeled Affibody Molecules Provide Superior HER3 Contrast to 89Zr-Labeled Antibody and Antibody-Fragment-Based Tracers
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. General
2.2. Generation of Seribantumab-F(ab’)2 and DFO Conjugation
2.3. Conjugation of DFO to Seribantumab and Seribantumab-F(ab’)2
2.4. Kinetic Evaluation of Seribantumab and Seribantumab-F(ab’)2
2.5. Radiolabeling of DFO-Seribantumab and DFO-Seribantumab-F(ab’)2 with 89Zr and 68Ga
2.6. Stability of [89Zr]Zr-DFO-Seribantumab, [89Zr]Zr-DFO-Seribantumab-F(ab’)2, and [68Ga]Ga-DFO-Seribantumab-F(ab’)2
2.7. Production and Radiolabeling of [68Ga]Ga-ZHER3
2.8. In Vitro Characterization of [89Zr]Zr-DFO-Seribantumab, [89Zr]Zr-DFO-Seribantumab-F(ab’)2, and [68Ga]Ga-DFO-Seribantumab-F(ab’)2
2.9. Biodistribution and In Vivo Specificity of [68Ga]Ga-DFO-Seribantumab-F(ab’)2, [89Zr]Zr-DFO-Seribantumab-F(ab’)2, and [89Zr]Zr-DFO-Seribantumab
2.10. Ex Vivo Autoradiography and Hematoxylin and Eosin Staining of BxPC-3 Xenografts
2.11. nanoPET/CT Imaging
3. Results
3.1. Generation of Seribantumab-F(ab’)2 and DFO Conjugation
3.2. Kinetic Evaluation of Seribantumab-F(ab’)2 and Seribantumab
3.3. Radiolabeling and Stability
3.4. In Vitro Characterization of [89Zr]Zr-DFO-Seribantumab, [89Zr]Zr-DFO-Seribantumab-F(ab’)2, and [68Ga]Ga-DFO-Seribantumab-F(ab’)2
3.5. In Vivo Biodistribution and Specificity
3.6. Ex Vivo Autoradiography of BxPC-3 Xenografts
3.7. nanoPET/CT Imaging
4. Discussion
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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Radioconjugate | Radiochemical Yield (%) (n = 3) | Purity (%) | Stability PBS (%) | Stability Serum 37 °C (%) | ||||
---|---|---|---|---|---|---|---|---|
1 h | 3 h | 24 h | 1 h | 3 h | 24 h | |||
[89Zr]Zr-DFO-seribantumab | 99.7 ± 0.5 | - | 100 ± 0 | 100.0 ± 0.1 | 100 ± 0 | 97.0 ± 0.7 | 92 ± 3 | 76 ± 4 |
[89Zr]Zr-DFO-seribantumab-F(ab’)2 | 80 ± 4 | 97 ± 1 | 97.1 ± 0.6 | 96.4 ± 0.8 | 92.4 ± 1.0 | 94.1 ± 0.8 | 93 ± 2 | 77 ± 6 |
[68Ga]Ga-DFO-seribantumab-F(ab’)2 | 88 ± 2 | 100 ± 0 | 100 ± 0 | 100 ± 0 | - | 15 ± 2 | 17 ± 3 | - |
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Rinne, S.S.; Leitao, C.D.; Abouzayed, A.; Vorobyeva, A.; Tolmachev, V.; Ståhl, S.; Löfblom, J.; Orlova, A. HER3 PET Imaging: 68Ga-Labeled Affibody Molecules Provide Superior HER3 Contrast to 89Zr-Labeled Antibody and Antibody-Fragment-Based Tracers. Cancers 2021, 13, 4791. https://doi.org/10.3390/cancers13194791
Rinne SS, Leitao CD, Abouzayed A, Vorobyeva A, Tolmachev V, Ståhl S, Löfblom J, Orlova A. HER3 PET Imaging: 68Ga-Labeled Affibody Molecules Provide Superior HER3 Contrast to 89Zr-Labeled Antibody and Antibody-Fragment-Based Tracers. Cancers. 2021; 13(19):4791. https://doi.org/10.3390/cancers13194791
Chicago/Turabian StyleRinne, Sara S., Charles Dahlsson Leitao, Ayman Abouzayed, Anzhelika Vorobyeva, Vladimir Tolmachev, Stefan Ståhl, John Löfblom, and Anna Orlova. 2021. "HER3 PET Imaging: 68Ga-Labeled Affibody Molecules Provide Superior HER3 Contrast to 89Zr-Labeled Antibody and Antibody-Fragment-Based Tracers" Cancers 13, no. 19: 4791. https://doi.org/10.3390/cancers13194791