89Zr-Immuno-PET with Immune Checkpoint Inhibitors: Measuring Target Engagement in Healthy Organs
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. 89Zr-mAb Studies
2.2. Biodistribution Analyses
2.3. Blood Sampling
2.4. Patlak Analysis
3. Results
3.1. Finding an Adequate Imaging Dose for 89Zr-Immuno-PET Imaging: [89Zr]Zr-Durvalumab as an Example
3.2. Measuring Target-Specific Irreversible Uptake Using Patlak Analyses
3.2.1. Spleen
3.2.2. Bone Marrow
3.2.3. Kidneys
3.2.4. Brain
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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89Zr-Immuno-PET Tracer | Target | Antibody Isotype | Mass Doses and Scan and Sample Time Points (h p.i.) | N | Tumour Type | References |
---|---|---|---|---|---|---|
[89Zr]Zr-nivolumab | PD-1 | IgG4 | 2 mg: 1, 72, 120, 168 3 mg/kg: 1, 72, 120, 168 | 3 3 | NSCLC | Niemeijer et al. [20] |
[89Zr]Zr-pembrolizumab | PD-1 | IgG4 | 2 mg: 1, 72, 120, 168 200 mg: 1, 48, 120, 168 | 3 3 | NSCLC | Niemeijer et al. [21] |
[89Zr]Zr-durvalumab | PD-L1 | IgG1 | 2 mg: 1, 72, 120, (168) * 22.5 mg: 48, 120, 168 750 mg: 1, 72, 120, (168) * | 11 4 10 | NSCLC | Smit et al. [22]; Pouw et al., manuscript in preparation |
[89Zr]Zr-BI 754111 | LAG-3 | IgG4 | 4 mg: 2, 96, 144 44 mg: 96, 144 604 mg: 96, 144 | 6 3 3 | NSCLC, HNSCC | Miedema et al. [15] |
[89Zr]Zr-ipilimumab | CTLA-4 | IgG1 | 10 mg: 72, (96,) 144 # 3 mg/kg: 72, 96, 144 | 9 3 | melanoma | Miedema et al. [23] |
Organ Tissue | Ns-Baseline Ki·10−3 [h−1] Median (IQ Range) |
---|---|
Kidney | 0.7 (0.4–1.3) |
Liver | 1.1 (0.8–2.1) |
Lung | 0.2 (0.1–0.3) |
Spleen | 0.5 (0.3–0.7) |
89Zr-Immuno-PET Tracer | Target | Mass Dose | Ki·10−3 [h−1] Median (IQ Range) | |||||||
---|---|---|---|---|---|---|---|---|---|---|
Spleen | N | Bone Marrow | N | Kidneys | N | Brain | N | |||
[89Zr]Zr-BI 754111 | LAG-3 | 4 mg | 26.3 (22.6–30.8) | 6 | 1.75 (1.38–2.20) | 6 | 1.62 (1.39–2.03) | 6 | 0.05 (0.01–0.11) | 6 |
44 mg | 2.10 (2.05–3.01) | 3 | 0.59 (0.47–0.63) | 3 | 0.43 (0.40–0.44) | 3 | 0.00 (0.00–0.02) | 3 | ||
604 mg | 0.54 (0.38–0.82) | 3 | 0.25 (0.18–0.32) | 3 | 0.51 (0.38–0.52) | 3 | 0.09 (0.05–0.10) | 3 | ||
[89Zr]Zr-durvalumab | PD-L1 | 2 mg | 12.1 (9.41–21.8) * | 4 | 2.40 (2.31–3.04) * | 4 | 1.84 (0.66–2.42) * | 9 | 0.03 (−0.05–0.18) * | 9 |
22.5 mg | 2.73 (2.33–3.06) * | 3 | 0.72 (0.61–0.74) | 4 | 1.07 (1.01–1.11) | 4 | 0.03 * | 1 | ||
750 mg | 0.77 (0.38–1.02) * | 8 | 0.63 (0.38–1.12) * | 8 | 0.67 (0.61–0.70) | 9 | 0.09 (0.01–0.13) | 9 | ||
[89Zr]Zr-nivolumab | PD-1 | 2 mg | 2.66 (2.29–3.68) | 3 | 1.29 (1.18–1.37) | 3 | 0.79 (0.65–1.03) | 3 | 0.11 (0.11–0.14) | 3 |
3 mg/kg | 0.58 (0.48–0.67) * | 2 | 0.54 (0.43–0.64) * | 2 | 0.26 (0.26–0.45) | 3 | 0.07 (0.07–0.12) | 3 | ||
[89Zr]Zr-pembrolizumab | PD-1 | 2 mg | 3.21 (2.85–3.29) | 3 | 3.45 * | 1 | 0.98 (0.94–1.11) | 3 | 0.12 (0.07–0.15) | 3 |
200 mg | 0.70 (0.69–0.71) | 3 | 0.22 (0.20–0.24) * | 2 | 0.46 (0.34–0.48) | 3 | 0.12 (0.06–0.15) | 3 | ||
[89Zr]Zr-ipilimumab | CTLA-4 | 10 mg | 0.15 (0.09–0.37) * | 7 | 0.31 (0.30–0.52) * | 7 | 0.72 (0.62–0.81) | 9 | 0.09 (−0.01–0.20 )* | 6 |
3 mg/kg | 0.43 (0.41–0.45) * | 2 | 0.19 * | 1 | 0.40 (0.38–0.41) * | 2 | −0.03 * | 1 |
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Miedema, I.H.C.; Wijngaarden, J.E.; Pouw, J.E.E.; Zwezerijnen, G.J.C.; Sebus, H.J.; Smit, E.; de Langen, A.J.; Bahce, I.; Thiele, A.; Vugts, D.J.; et al. 89Zr-Immuno-PET with Immune Checkpoint Inhibitors: Measuring Target Engagement in Healthy Organs. Cancers 2023, 15, 5546. https://doi.org/10.3390/cancers15235546
Miedema IHC, Wijngaarden JE, Pouw JEE, Zwezerijnen GJC, Sebus HJ, Smit E, de Langen AJ, Bahce I, Thiele A, Vugts DJ, et al. 89Zr-Immuno-PET with Immune Checkpoint Inhibitors: Measuring Target Engagement in Healthy Organs. Cancers. 2023; 15(23):5546. https://doi.org/10.3390/cancers15235546
Chicago/Turabian StyleMiedema, Iris H. C., Jessica E. Wijngaarden, Johanna E. E. Pouw, Gerben J. C. Zwezerijnen, Hylke J. Sebus, Egbert Smit, Adrianus J. de Langen, Idris Bahce, Andrea Thiele, Daniëlle J. Vugts, and et al. 2023. "89Zr-Immuno-PET with Immune Checkpoint Inhibitors: Measuring Target Engagement in Healthy Organs" Cancers 15, no. 23: 5546. https://doi.org/10.3390/cancers15235546
APA StyleMiedema, I. H. C., Wijngaarden, J. E., Pouw, J. E. E., Zwezerijnen, G. J. C., Sebus, H. J., Smit, E., de Langen, A. J., Bahce, I., Thiele, A., Vugts, D. J., Boellaard, R., Huisman, M. C., & Menke-van der Houven van Oordt, C. W. (2023). 89Zr-Immuno-PET with Immune Checkpoint Inhibitors: Measuring Target Engagement in Healthy Organs. Cancers, 15(23), 5546. https://doi.org/10.3390/cancers15235546