Article Figures & Data
Figures
- FIGURE 1.
(A–C) Lindmo plots showing in vitro binding of 125I-DS-8895a (A), 111In-CHX-A″-DTPA-DS-8895a (B), and 89Zr-Df-Bz-NCS-DS-8895a (C) to increasing concentrations of EphA2-positive MDA-MB-231 cells. (D–F) Scatchard plots showing in vitro binding of 125I-DS-8895a (D), 111In-CHX-A″-DTPA-DS-8895a (E), and 89Zr-Df-Bz-NCS-DS-8895a (F) to MDA-MB-231 cells.
- FIGURE 2.
Biodistribution properties of 125I-DS-8895a (A), 111In-CHX-A″-DTPA-DS-8895a (B), and 89Zr-Df-Bz-NCS-DS-8895a (C) in MDA-MB-231–xenografted BALB/c nu/nu mice. Bars indicate mean ± SD (n = 5).
- FIGURE 3.
Biodistribution properties of 89Zr-Df-Bz-NCS-DS-8895a in BALB/c nu/nu mice bearing EphA2-positive MDA-MB-231 breast tumors (A) and EphA2-negative CCRF-CEM human lymphoblastic leukemia (B) on days 2 and 7 after injection. Bars indicate mean ± SD (n = 5).
- FIGURE 4.
(A) MR (surface-rendered), SPECT (maximum-intensity projection), and fused SPECT/MR images of MDA-MB-231–xenografted mice at 2 h (day 0), 3 d, and 7 d after injection of 111In-CHX-A″-DTPA-DS-8895a. (B) MR (surface-rendered), PET (maximum-intensity projection), and fused PET/MR images of MDA-MB-231–xenografted mice at 2 h (day 0), 2 d, and 7 d after injection of 89Zr-Df-Bz-NCS-DS-8895a.
- FIGURE 5.
Influence of cold-dose DS-8895a on tumor uptake of 89Zr-Df-Bz-NCS-DS-8895a in BALB/c nu/nu mice bearing MDA-MB-231 xenografts on days 2 (A) and 7 (B) after injection, and tumor-to-blood ratios on days 2 (C) and 7 (D) after injection. There was no significant difference in average tumor size among the various dose levels on days 2 (E) and 7 (F) after injection. Bars indicate mean ± SD (n = 5). *P < 0.05. **P < 0.005. ***P < 0.0005. ****P < 0.0001.
- FIGURE 6.
In vivo saturation of 89Zr-labeled DS-8895a as demonstrated by PET/MR on days 2 (A) and 7 (B) after injection. Representative whole-body surface-rendered MR images, maximum-intensity-projection PET images, and fused PET/MR images are shown for each time point with different dose levels of cold DS-8895a (0.3, 3, and 30 mg/kg). Hot spot in tumor on day 7 PET and PET/MR images of mouse receiving 30 mg/kg is due to blood crust.
Tables
- TABLE 1
Pharmacokinetic Parameters of 89Zr- and 111In-Labeled DS-8895a in MDA-MB-231 Tumor–Bearing Mice
Parameter 89Zr-labeled DS-8895a 111In-labeled DS-8895a P AUC (h × μg/mL) 185.7 ± 26.96 417.6 ± 90.60 0.0033 t1/2α (h) 1.48 ± 0.26 8.85 ± 4.97 0.0295 t1/2β (h) 102.4 ± 14.65 215.1 ± 72.88 0.0244 Cmax (μg/mL) 3.03 ± 0.43 2.07 ± 0.29 0.0033 CL (mL/h) 0.027 ± 0.004 0.012 ± 0.002 <0.0001 Vss (mL) 3.90 ± 0.11 3.59 ± 0.43 0.1845 AUC = area under curve; t1/2α = half-life of initial phase of disposition; t1/2β = half-life of terminal phase of disposition; Cmax = maximum plasma-serum concentration; CL = total serum clearance; Vss = volume of distribution at steady state.
Data are mean ± SD (n = 5). P values are result of unpaired t test; Welch correction was used when variances were significantly different.
