Article Figures & Data
Figures
- FIGURE 1.
Biodistribution of 89Zr-labeled mAb: physiologic components. (A) Reversible nonspecific uptake due to antibody in vascular tissue compartment and antibody entering tissue interstitium through paracellular pores, and through endothelial cells mediated by neonatal Fc-receptor, leaving tissue by convective transport through lymph flow. (B) Irreversible nonspecific uptake due to mAb degradation in lysosome, followed by residualization of 89Zr. (C) Specific uptake due to target engagement (target binding and internalization of mAb-target antigen). (Adapted from Lobo et al. (8) and Chen et al. (10).)
- FIGURE 2.
Transfer constants for 89Zr-anti-HER2 in kidney. (A and B) Example for 1 patient in 89Zr-anti-HER2 study, with measured activity concentrations in serum (A) and measured activity concentrations in kidney (B). (C) Patlak linearization to determine offset (VT) and slope (Ki) of linear fit to last 3 time points (same data). (D) Reversible and irreversible contributions to total measured signal. No target expression has been reported for HER2 in normal kidney. Therefore, we hypothesize that total signal consists of nonspecific uptake. After 100 h after injection, total uptake predominantly consists of irreversible nonspecific uptake due to 89Zr-residualization after mAb degradation. p.i. = after injection.
- FIGURE 3.
Transfer constants for 89Zr-anti-PSMA in kidney. (A and B) Example for 1 patient in 89Zr-anti-PSMA study, with measured activity concentrations in serum (A) and measured activity concentrations in kidney (B). (C) Patlak linearization to determine offset (VT) and slope (Ki) of linear fit to last 3 time points (same data). (D) Total reversible and total irreversible contributions to measured signal. Dashed lines represent estimated values for nonspecific reversible uptake (calculated as baseline
) and nonspecific irreversible uptake (calculated as baseline ). Nonspecific uptake accounts for 66%, 34%, and 22% of total measured signal at 1, 3, and 7 d after injection, respectively. Difference between total irreversible uptake and estimated nonspecific irreversible uptake indicates target-mediated uptake. p.i. = after injection.
Tables
Characteristic 89Zr-anti-CD20 89Zr-anti-EGFR 89Zr-anti-PSMA 89Zr-anti-HER2 mAb Obinutuzumab Cetuximab Hu-J591 Trastuzumab Type Humanized Chimeric Humanized Humanized IgG subclass IgG1 IgG1 IgG1 IgG1 Target expression (20) Kidney Absent Absent Present Absent Liver Absent Present Present Present Lung Absent Absent Absent Present Spleen Present Absent Absent* Absent Center Amsterdam UMC (n = 4); CHU Lille (n = 5) Amsterdam UMC Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center Patient category Non-Hodgkin lymphoma Colorectal carcinoma Prostate cancer Gastric cancer Number of patients 9 7 10 10 Injected activity/mAb dose 37 MBq/10 mg; 1,000 mg unlabeled mAb 37 MBq/10 mg; 500 mg/m2 unlabeled mAb 185 MBq/1.7 mg; total mass of 25 mg mAb 185 MBq/3 mg; total mass of 50 mg mAb Administration† Predose Predose Coinjection Coinjection PET scan time points 1 h, 72 h, 144 h after injection 1 h, 72 h, 144 h after injection 2–4 h, 24 h, 48–120 h, 144–168 h after injection 4 h, 24 h, 48–96 h, 120–192 h after injection Blood sample‡ Plasma Plasma Serum Serum Blood sampling time points 5, 30, 60, 120 min; 24¶, 72, 144 h after injection 1–2, 24, 48, 72, 144 h 5, 30, 60, 120–240 min; 24, 48–120, 144–168 h after injection 5, 15, 30, 60 min; 2, 24,48–96, 120–192 h after injection Reference Jauw et al. (16) Menke et al. (17) Pandit-Taskar et al. (18) O’Donoghue et al. (19) ↵* Expression of prostate-specific membrane antigen in spleen has been reported (24).
↵† Predose = 89Zr-mAb within 2 h after administration of unlabeled mAb.
↵‡ Blood samples consisted of plasma or serum samples, assuming no practical difference between these assays for our purposes because mAb binding does not occur to coagulation factors (difference between plasma and serum).
↵¶ Blood samples obtained at 24 h after injection at CHU Lille (n = 5); no 24-h sample obtained at Amsterdam UMC.
Coinjection = unlabeled mAb infused intravenously over 5 min followed immediately by 1 min infusion of radiolabeled mAb.
Site 89Zr-anti-CD20 89Zr-anti-EGFR 89Zr-anti-PSMA 89Zr-anti-HER2 Baseline Kidney 0.18 (0.15–020) 0.25 (0.23–0.29) 0.28 (0.21–0.32) 0.19 (0.15–0.25) 0.20 (0.16–0.25) Liver 0.24 (0.21–0.28) 0.64 (0.54–0.91) 0.29 (0.23–0.43) 0.24 (0.22–0.29) 0.24 (0.21–0.28) Lung 0.08 (0.08–0.10) 0.11 (0.09–0.13) 0.07 (0.06–0.09) 0.08 (0.05–0.11) 0.09 (0.07–0.10) Spleen 0.20 (0.18–0.21) 0.23 (0.20–0.27) 0.22 (0.20–0.28) 0.24 (0.18–0.27) 0.24 (0.20–0.27) Vt (mL⋅cm−3) is presented as median followed by IQ in parentheses.
Site 89Zr-anti-CD20 89Zr-anti-EGFR 89Zr-anti-PSMA 89Zr-anti-HER2 Baseline Kidney 0.4 (0.2–0.6) 0.7 (0.4–1.2) 2.8 (2.4–3.1) 1.5 (0.9–1.8) 0.7 (0.4–1.3) Liver 1.1 (0.8–2.1) 3.8 (1.9–5.8) 5.7 (4.9–8.4) 1.7 (1.4–2.0) 1.1 (0.8–2.1) Lung 0.2 (0.1–0.3) 0.4 (0.2–0.6) 0.1 (0.0–0.2) 0.2 (0.0–0.5) 0.2 (0.1–0.3) Spleen 0.6 (0.5–0.8) 0.5 (0.3–0.5) 1.5 (1.2–1.7) 0.7 (0.4–0.8) 0.5 (0.3–0.7) Ki (μL⋅g−1⋅h−1) is presented as median followed by IQ in parentheses.
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