Article Figures & Data
Figures
- FIGURE 1.
RP-HPLC analysis of [111In]Z-070 (A) and [99mTc]Demobesin 1 (B).
- FIGURE 2.
Comparison of [111In]Z-070 internalization rate in rat acinar pancreatic tumor AR4-2J cells and in human prostate adenocarcinoma PC-3 cells. Data were acquired from 2 independent experiments in triplicates and are expressed as specific internalization per million cells.
Tables
Peptide UV/Vis detection tR (min) γ-Detection tR (min) System 1 System 2 System 1 System 2 Z-070 ND 18.3 ND ND [111In]Z-070 ND ND ND 18.4 [InIII]Z-070 ND 18.4 ND ND [YIII]Z-070 ND 18.4 ND ND [LuIII]Z-070 ND 18.4 ND ND Demobesin 1 12.3 16.3 ND ND [99mTc]Demobesin 1 ND ND 14.3 ND [ReV]Demobesin 1 13.8 19.2 ND ND UV/Vis = UV visible; ND = not done.
Runs were conducted on a Waters XTerra RP-8 cartridge column (5 μm, 150 × 4.6 mm) at 1-mL/min flow rate adopting a linear gradient system starting from 15% solvent A (acetonitrile) and 85% solvent B (0.1% TFA in water) and reaching 75% solvent A and 25% solvent B within 30 min for system 1 and 60 min for system 2.
- TABLE 2
Binding Affinity (IC50 in nmol/L [mean ± SEM]) to Human GRP-R and Mouse or Rat GRP-R of Bombesin Analogs
Peptide Membrane-binding assay Receptor autoradiography Human R (PC-3) Rodent R (AR4-2J) Human R (prostate cancer) Rodent R (mouse pancreas) [Tyr4]BB 0.87 ± 0.32 (2) 0.25 ± 0.18 (3) 1.1 ± 0.0 (3) ND Demobesin 1 0.35 ± 0.33 (3) 0.45 ± 0.18 (2) 3.2 ± 0.7 (5) 7.1 ± 1.1 (3) Z-070 5.14 ± 3.27 (3) 0.37 ± 0.15 (3) 8.3 ± 1.9 (3) 0.76 ± 0.18 3 (3) [InIII]Z-070 3.87 ± 0.97 (3) 0.17 ± 0.04 (3) ND ND [YIII]Z-070 3.93 ± 1.23 (3) 0.20 ± 0.00 (3) 6.3 ± 1.3 (5) 0.46 ± 0.03 (3) [LuIII]Z-070 ND ND 6.6 ± 2 (3) 0.5 ± 0.1 (3) ND = not done.
Value in parentheses is number of independent studies.
- TABLE 3
Biodistribution Analysis (%ID/g ± SD, n = 4) and Tissue Ratios of [111In]Z-070 in AR4-2J Tumor-Bearing Lewis Rats
Site %ID/g Tissue ratio 4 h 24 h 4 h 4 h, blocked* 24 h Blood 0.014 ± 0.005 0.010 ± 0.001 0.004 ± 0.001 Tumor/blood 111 252 Muscle 0.021 ± 0.004 0.019 ± 0.008 0.022 ± 0.008 Tumor/muscle 74 46 Tumor 1.55 ± 0.25 0.14 ± 0.02 1.01 ± 0.07 Tumor/liver 22 25 Kidney 0.76 ± 0.18 0.62 ± 0.11 0.60 ± 0.05 Tumor/kidney 2.0 1.7 Adrenal 0.33 ± 0.05 0.11 ± 0.04 0.26 ± 0.08 Pancreas 4.29 ± 0.61 0.11 ± 0.01 3.71 ± 0.26 Spleen 0.05 ± 0.01 0.05 ± 0.00 0.04 ± 0.01 Stomach 0.15 ± 0.03 0.05 ± 0.02 0.11 ± 0.01 Bowel 0.31 ± 0.09 0.05 ± 0.01 0.14 ± 0.03 Liver 0.07 ± 0.02 0.08 ± 0.00 0.04 ± 0.00 Lung 0.03 ± 0.01 0.03 ± 0.00 0.02 ± 0.00 Heart 0.01 ± 0.00 0.01 ± 0.00 0.01 ± 0.00 Bone 0.02 ± 0.01 0.01 ± 0.00 0.01 ± 0.01 ↵* Blocked by injecting 50 μg BZH2 together with radiopeptide.
- TABLE 4
Biodistribution of [111In]Z-070 in Double (Rat AR4-2J and Human PC-3) Tumor-Bearing Athymic Mice
Organ Time after injection 1 h 4 h 24 h Blood 0.78 ± 0.25 0.38 ± 0.27 0.40 ± 0.50 Liver 0.95 ± 0.19 0.55 ± 0.07 0.28 ± 0.04 Heart 0.84 ± 0.25 0.49 ± 0.12 0.30 ± 0.01 Kidneys 9.37 ± 3.80 5.49 ± 1.99 0.78 ± 0.18 Stomach 1.52 ± 0.24 0.68 ± 0.13 0.16 ± 0.08 Intestine 6.41 ± 0.59 6.78 ± 1.49 1.30 ± 0.11 Spleen 1.21 ± 0.38 1.07 ± 0.31 0.28 ± 0.04 Muscle 0.56 ± 0.19 0.33 ± 0.03 0.33 ± 0.08 Lung 1.23 ± 0.38 0.38 ± 0.04 0.48 ± 0.23 Pancreas 43.04 ± 13.44 25.36 ± 1.43 2.16 ± 0.68 AR4-2J tumor 3.24 ± 0.72 2.72 ± 0.56 1.87 ± 0.37 PC-3 tumor 4.67 ± 1.60 2.57 ± 0.56 1.19 ± 0.27 Organ Blocking at 4 h after injection* 100 μg 250 μg Stomach 1.17 ± 0.56 1.37 ± 0.47 Intestine 1.40 ± 0.21 1.53 ± 0.36 Pancreas 1.44 ± 0.13 1.14 ± 0.13 AR4-2J tumor 1.88 ± 0.59 1.22 ± 0.22 PC-3 tumor 3.00 ± 1.26 1.85 ± 0.12 ↵* Blocking by coinjection of 100 or 250 μg [Tyr4]BB.
- TABLE 5
Biodistribution of [99mTc]Demobesin 1 in Double (Rat AR4-2J and Human PC-3) Tumor-Bearing Athymic Mice
Organ Time after injection 1 h 4 h 24 h Blood 1.20 ± 0.27 0.29 ± 0.10 0.09 ± 0.09 Liver 5.92 ± 1.0 4.71 ± 1.1 0.59 ± 0.10 Heart 0.91 ± 0.18 0.27 ± 0.17 0.08 ± 0.02 Kidneys 8.10 ± 1.34 5.76 ± 1.95 0.49 ± 0.14 Stomach 3.91 ± 0.54 2.79 ± 0.55 0.18 ± 0.10 Intestine 11.99 ± 0.87 12.18 ± 1.60 0.59 ± 0.11 Spleen 1.00 ± 0.29 0.41 ± 0.12 0.12 ± 0.02 Muscle 0.50 ± 0.36 0.09 ± 0.03 0.06 ± 0.02 Lung 1.66 ± 0.36 0.41 ± 0.07 0.67 ± 0.99 Pancreas 82.30 ± 9.46 35.28 ± 10.66 0.76 ± 0.25 AR4-2J tumor 4.42 ± 0.91 2.78 ± 0.67 0.71 ± 0.09 PC-3 tumor 13.45 ± 3.04 9.42 ± 0.65 2.17 ± 0.63 Organ Blocking at 4 h after injection* 100 μg 250 μg Stomach 2.82 ± 1.15 2.09 ± 0.50 Intestine 7.77 ± 1.11 5.55 ± 0.72 Pancreas 7.20 ± 1.12 3.78 ± 1.37 AR4-2J tumor 3.16 ± 0.60 1.60 ± 0.09 PC-3 tumor 4.75 ± 0.91 2.27 ± 0.32 ↵* Blocking by coinjection of 100 or 250 μg [Tyr4]BB.
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