Article Figures & Data
Figures
- FIGURE 1.
Schematic structures of HYNIC-linker-Nle-CycMSHhex.
- FIGURE 2.
In vitro competitive binding curves of HYNIC-PEG2Nle-CycMSHhex (●, IC50 = 0.3 ± 0.06 nM), HYNIC-AocNle-CycMSHhex (▲, IC50 = 0.4 ± 0.08 nM), HYNIC-GGGNle-CycMSHhex (▪, IC50 = 0.7 ± 0.1 nM), and HYNIC-GSGNle-CycMSHhex (♦, IC50 = 0.8 ± 0.09 nM) in B16/F1 murine melanoma cells.
- FIGURE 3.
Representative whole-body (A), coronal (B), and transversal (C) SPECT/CT images of 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex in B16/F1 melanoma–bearing C57 mouse at 2 h after injection. K = kidney; T = tumor.
- FIGURE 4.
Comparison of tumor-to-kidney ratios between 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex and 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex at 0.5, 2, 4, and 24 h after injection. Data on 99mTc(EDDA)-HYNIC-GGNle-CycMSHhex (12) are shown for comparison.
Tables
Peptide IC50 (nM) Calculated MW Measured MW HYNIC-GGNle-CycMSHhex* 0.6 ± 0.04 1,232.4 1,232.8 HYNIC-GGGNle-CycMSHhex 0.7 ± 0.1 1,288.0 1,288.2 HYNIC-GSGNle-CycMSHhex 0.8 ± 0.09 1,318.0 1,318.9 HYNIC-PEG2Nle-CycMSHhex 0.3 ± 0.06 1,262.0 1,261.8 HYNIC-AocNle-CycMSHhex 0.4 ± 0.08 1,257.0 1,257.3 ↵* Data are shown for comparison (12).
MW = molecular weight.
- TABLE 2
Biodistribution Comparison Among Peptides in B16/F1 Melanoma–Bearing C57 Mice 2 Hours After Injection
Tissue GGG GSG PEG2 Aoc %ID/g Tumor 9.78 ± 3.40 7.41 ± 4.26 14.32 ± 2.82 22.3 ± 1.72 Brain 0.05 ± 0.03 0.07 ± 0.11 0.03 ± 0.02 0.04 ± 0.04 Blood 0.07 ± 0.01 0.08 ± 0.06 0.39 ± 0.07 0.28 ± 0.01 Heart 0.04 ± 0.03 0.06 ± 0.02 0.08 ± 0.03 0.20 ± 0.10 Lung 0.18 ± 0.12 0.15 ± 0.05 0.27 ± 0.12 0.38 ± 0.19 Liver 0.26 ± 0.03 0.23 ± 0.01 0.33 ± 0.03 0.81 ± 0.03 Spleen 0.16 ± 0.09 0.08 ± 0.02 0.11 ± 0.08 0.24 ± 0.00 Stomach 0.43 ± 0.27 0.48 ± 0.39 0.43 ± 0.05 0.70 ± 0.36 Kidneys 5.09 ± 2.19 3.90 ± 1.01 5.79 ± 1.79 6.52 ± 1.04 Muscle 0.03 ± 0.03 0.05 ± 0.02 0.03 ± 0.01 0.06 ± 0.05 Pancreas 0.02 ± 0.01 0.02 ± 0.02 0.08 ± 0.06 0.09 ± 0.00 Bone 0.08 ± 0.06 0.12 ± 0.13 0.29 ± 0.14 0.27 ± 0.10 Skin 0.31 ± 0.10 0.22 ± 0.06 0.49 ± 0.07 0.43 ± 0.11 %ID Intestines 0.52 ± 0.09 0.72 ± 0.27 0.99 ± 0.55 1.85 ± 0.51 Urine 93.90 ± 1.47 95.25 ± 0.52 93.19 ± 1.91 88.46 ± 2.23 T/NT Liver 37.26 32.26 43.14 27.51 Kidney 1.92 1.90 2.48 3.42 Lung 54.44 50.07 53.72 57.99 Muscle 351.42 146.90 465.25 378.94 Blood 147.62 98.05 36.80 79.79 Skin 31.75 34.01 29.40 52.23 GGG = 99mTc(EDDA)-HYNIC-GGGNle-CycMSHhex; GSG = 99mTc(EDDA)-HYNIC-GSGNle-CycMSHhex; PEG2 = 99mTc(EDDA)-HYNIC-PEG2Nle-CycMSHhex; Aoc = 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex; T/NT = tumor–to–normal-tissue uptake ratio.
Data are %ID/g or %ID (mean ± SD, n = 5).
- TABLE 3
Biodistribution of 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex in B16/F1 Melanoma–Bearing C57 Mice
Tissue 0.5 h 2 h 4 h 24 h 2-h NDP blockade 2-h L-lys coinjection %ID/g Tumor 23.44 ± 3.37 22.8 ± 1.71 22.17 ± 5.93 7.13 ± 0.99 1.26 ± 0.59* 25.85 ± 6.8 Brain 0.17 ± 0.07 0.05 ± 0.03 0.02 ± 0.02 0.01 ± 0.01 0.03 ± 0.01 0.03 ± 0.01 Blood 2.98 ± 1.77 0.40 ± 0.14 0.30 ± 0.14 0.09 ± 0.03 0.82 ± 0.15 0.18 ± 0.13 Heart 1.75 ± 0.31 0.23 ± 0.08 0.13 ± 0.09 0.07 ± 0.02 0.32 ± 0.09 0.14 ± 0.01 Lung 4.06 ± 1.60 0.52 ± 0.20 0.50 ± 0.19 0.14 ± 0.02 0.91 ± 0.06 0.59 ± 0.06 Liver 3.19 ± 0.39 1.09 ± 0.33 1.26 ± 0.60 0.36 ± 0.01 1.22 ± 0.12 1.22 ± 0.15 Spleen 0.94 ± 0.72 0.30 ± 0.13 0.32 ± 0.13 0.05 ± 0.04 0.17 ± 0.11 0.22 ± 0.09 Stomach 2.52 ± 0.22 1.07 ± 0.10 0.73 ± 0.21 0.11 ± 0.02 0.56 ± 0.10 0.97 ± 0.36 Kidneys 19.65 ± 7.36 6.92 ± 1.40 6.10 ± 0.72 1.05 ± 0.07 6.05 ± 1.13 4.64 ± 0.48* Muscle 0.43 ± 0.14 0.04 ± 0.03 0.04 ± 0.03 0.02 ± 0.01 0.06 ± 0.05 0.07 ± 0.06 Pancreas 0.97 ± 0.40 0.19 ± 0.14 0.44 ± 0.64 0.06 ± 0.03 0.31 ± 0.10 0.06 ± 0.02 Bone 1.09 ± 0.28 0.15 ± 0.09 0.19 ± 0.15 0.12 ± 0.07 0.30 ± 0.08 0.33 ± 0.30 Skin 3.62 ± 0.35 0.46 ± 0.10 0.37 ± 0.11 0.15 ± 0.05 0.45 ± 0.06 0.54 ± 0.10 %ID Intestines 2.43 ± 0.31 1.85 ± 0.51 3.43 ± 0.76 0.32 ± 0.09 1.85 ± 0.42 1.64 ± 0.40 Urine 60.22 ± 4.46 88.46 ± 2.23 84.47 ± 4.80 96.84 ± 1.17 91.29 ± 0.70 88.11 ± 1.90 T/NT Liver 7.34 20.86 17.62 20.05 1.03 21.19 Kidney 1.19 3.29 3.63 6.78 0.21 5.57 Lung 5.78 43.77 44.51 52.05 1.39 44.16 Muscle 54.62 527.80 502.79 450.68 21.12 392.26 Blood 7.87 57.59 74.61 82.89 1.54 139.85 Skin 6.47 49.13 59.92 47.99 2.82 47.44 ↵* P < 0.05 for differences in tumor and kidney uptake between 99mTc(EDDA)-HYNIC-AocNle-CycMSHhex with and without peptide blockade, and with and without L-lys coinjection at 2 h after injection.
T/NT = tumor–to–normal-tissue uptake ratio.
Two-hour data are cited from Table 2 for comparison. Data are %ID/g or %ID (mean ± SD, n = 5).
