Article Figures & Data
Figures
- FIGURE 1.
Structures and synthesis of DOTA–PNA–peptide conjugates.
- FIGURE 2.
Somatostatin receptor binding of 111In-DOTA-anti-bcl-2-PNA-Tyr3-octreotate and 111In-DOTA-Tyr3-octreotate in Mec-1 cells.
- FIGURE 3.
Uptake and blocking of 111In-DOTA–PNA–peptide conjugates in Mec-1 cells (n = 3).
- FIGURE 4.
Internalization of 111In-DOTA–PNA–peptide conjugates in Mec-1 cells (n = 3).
- FIGURE 5.
Efflux of 111In-DOTA–PNA–peptide conjugates in Mec-1 cells (n = 3).
- FIGURE 6.
Western blot analysis of bcl-2 protein synthesis. Lane 1, untreated control; lane 2, cells treated with compound 1; lane 3, untreated control; lane 4, cells treated with compound 2; lane 5, cells treated with compound 3.
- FIGURE 7.
(Top) MicroSPECT/CT images of 111In-DOTA–PNA–peptide conjugates in Mec-1–bearing SCID mice (n = 3). (A) 111In-DOTA-Tyr3-octreotate (1 h). (B) 111In-DOTA-anti-bcl-2-PNA-Tyr3-octreotate (48 h). (C) 111In-DOTA-nonsense-PNA-Tyr3-octreotate (48 h). (D) 111In-DOTA-anti-bcl-2-PNA-Ala[3,4,5,6] (48 h). (Bottom) Corresponding transaxial slices through the centers of the tumors.
Tables
- TABLE 1
Biodistribution of 111In-DOTA-Tyr3-Octreotate in SCID Mice Bearing Mec-1 SLL Xenografts (n = 5)
Biodistribution (%ID/g ± SD) Tissue 1 h 4 h 24 h Blood 0.31 ± 0.07 0.06 ± 0.01 0.02 ± 0.003 Lung 8.27 ± 1.88 6.87 ± 0.54 4.12 ± 0.84 Liver 0.32 ± 0.07 0.29 ± 0.06 0.20 ± 0.04 Spleen 0.63 ± 0.14 0.48 ± 0.10 0.44 ± 0.10 Kidney 11.4 ± 1.70 11.0 ± 1.46 6.39 ± 0.73 Bladder 5.18 ± 1.51 0.59 ± 0.21 0.22 ± 0.03 Muscle 0.04 ± 0.01 0.02 ± 0.002 0.01 ± 0.001 Fat 0.08 ± 0.026 0.03 ± 0.008 0.01 ± 0.003 Heart 0.26 ± 0.03 0.12 ± 0.02 0.07 ± 0.02 Bone 0.52 ± 0.10 0.57 ± 0.10 0.22 ± 0.05 Stomach 5.80 ± 1.47 5.14 ± 1.26 1.87 ± 0.31 Small intestine 1.70 ± 0.31 0.96 ± 0.009 0.40 ± 0.06 Large intestine 2.06 ± 0.33 5.25 ± 0.84 1.09 ± 0.25 Tumor 3.24 ± 0.77 3.24 ± 0.85 1.49 ± 0.29 - TABLE 2
Biodistribution of 111In-DOTA-Anti-bcl-2-PNA-Tyr3-Octreotate in SCID Mice Bearing Mec-1 SLL Xenografts (n = 5)
Biodistribution (%ID/g ± SD) Tissue 1 h 4 h 24 h 48 h Blood 2.56 ± 0.21 2.38 ± 0.46 0.57 ± 0.12 0.19 ± 0.02 Lung 6.06 ± 1.20 2.56 ± 0.31 1.36 ± 0.29 1.97 ± 0.04 Liver 12.6 ± 2.03 6.70 ± 1.67 6.17 ± 1.36 6.12 ± 1.50 Spleen 2.75 ± 0.51 1.34 ± 0.04 1.36 ± 0.28 1.05 ± 0.06 Kidney 77.1 ± 16.5 129.4 ± 25.7 70.2 ± 5.73 32.8 ± 6.38 Bladder 1.71 ± 0.93 1.34 ± 0.29 0.84 ± 0.18 0.71 ± 0.18 Muscle 0.32 ± 0.02 0.20 ± 0.04 0.12 ± 0.02 0.12 ± 0.02 Fat 0.21 ± 0.04 0.29 ± 0.06 0.23 ± 0.05 0.16 ± 0.03 Heart 0.93 ± 0.12 0.99 ± 0.13 0.61 ± 0.12 0.34 ± 0.04 Bone 0.82 ± 0.13 0.41 ± 0.05 0.42 ± 0.08 0.35 ± 0.09 Stomach 2.12 ± 0.70 2.33 ± 0.79 1.02 ± 0.18 0.51 ± 0.14 Small intestine 1.24 ± 0.19 0.79 ± 0.21 0.32 ± 0.04 0.24 ± 0.04 Large intestine 1.19 ± 0.12 2.26 ± 0.47 0.48 ± 0.07 0.41 ± 0.10 Tumor 1.32 ± 0.08 1.40 ± 0.32 1.02 ± 0.18 0.88 ± 0.22 - TABLE 3
Biodistribution of 111In-DOTA-Nonsense-PNA-Tyr3- Octreotate in SCID Mice Bearing Mec-1 SLL Xenografts (n = 5)
Biodistribution (%ID/g ± SD) Tissue 4 h 24 h 48 h Blood 1.27 ± 0.30 0.25 ± 0.02 0.09 ± 0.01 Lung 1.23 ± 0.21 0.77 ± 0.15 0.51 ± 0.07 Liver 6.34 ± 1.19 5.74 ± 0.59 5.61 ± 0.70 Spleen 1.56 ± 0.23 1.70 ± 0.36 1.32 ± 0.16 Kidney 100.7 ± 23.3 76.1 ± 9.82 53.3 ± 6.06 Bladder 0.48 ± 0.01 0.57 ± 0.14 0.20 ± 0.06 Muscle 0.13 ± 0.03 0.08 ± 0.01 0.07 ± 0.01 Fat 0.14 ± 0.02 0.17 ± 0.04 0.07 ± 0.01 Heart 0.50 ± 0.08 0.26 ± 0.01 0.19 ± 0.01 Bone 0.30 ± 0.03 0.24 ± 0.05 0.18 ± 0.05 Stomach 0.17 ± 0.09 0.28 ± 0.05 0.20 ± 0.05 Small intestine 0.56 ± 0.13 0.18 ± 0.03 0.13 ± 0.02 Large intestine 2.15 ± 0.57 0.27 ± 0.05 0.18 ± 0.04 Tumor 0.89 ± 0.21 0.75 ± 0.13 0.57 ± 0.08 - TABLE 4
Biodistribution of 111In-DOTA-Anti-bcl-2-PNA-Ala[3,4,5,6] in SCID Mice Bearing Mec-1 SLL Xenografts (n = 5)
Biodistribution (%ID/g ± SD) Tissue 4 h 24 h 48 h Blood 0.14 ± 0.01 0.04 ± 0.006 0.02 ± 0.003 Lung 0.13 ± 0.02 0.08 ± 0.01 0.06 ± 0.01 Liver 0.24 ± 0.02 0.27 ± 0.03 0.23 ± 0.02 Spleen 0.09 ± 0.02 0.11 ± 0.01 0.12 ± 0.005 Kidney 7.06 ± 1.83 6.02 ± 0.88 2.26 ± 0.52 Bladder 0.06 ± 0.01 0.17 ± 0.03 0.10 ± 0.02 Muscle 0.02 ± 0.002 0.02 ± 0.004 0.01 ± 0.002 Fat 0.03 ± 0.006 0.02 ± 0.005 0.02 ± 0.005 Heart 0.06 ± 0.01 0.04 ± 0.01 0.03 ± 0.005 Bone 0.03 ± 0.003 0.02 ± 0.006 0.01 ± 0.001 Stomach 0.10 ± 0.002 0.03 ± 0.007 0.02 ± 0.001 Small intestine 0.06 ± 0.005 0.04 ± 0.004 0.02 ± 0.003 Large intestine 0.19 ± 0.01 0.05 ± 0.01 0.02 ± 0.005 Tumor 0.12 ± 0.01 0.07 ± 0.02 0.06 ± 0.01
