Article Figures & Data
Figures
- FIGURE 1.
Reported radiolabeled small-molecule inhibitors for CA-IX imaging. Compounds A–M are sulfonamide-based derivatives, whereas compound N is a coumarin-based inhibitor.
- FIGURE 2.
Synthesis of azidoacetyl-AEBS 1 (A), azidoacetyl-ABS 2 (B), AmBF3-AEBS and AmBF3-ABS (C), and AmBF3-(AEBS)3 and AmBF3-(ABS)3 (D). DCC = N,N′-dicyclohexylcarbodiimine; NHS = N-hydroxysuccinimde.
- FIGURE 3.
Radiosynthesis of 18F-AmBF3-AEBS and 18F-AmBF3-ABS (A) and 18F-AmBF3-(AEBS)3 and 18F-AmBF3-(ABS)3 (B) via 18F-19F isotope exchange reaction.
- FIGURE 4.
PET/CT images of monomeric 18F-sulfonamides at 1 h after injection of 18F-AmBF3-AEBS (A) and 18F-AmBF3-ABS (B). Tumors are indicated by arrows. Scale bar unit is %ID/g.
- FIGURE 5.
PET/CT images of trimeric 18F-sulfonamides at 1 h after injection of 18F-AmBF3-(AEBS)3 (A), 18F-AmBF3-(ABS)3 (B), and 18F-AmBF3-(ABS)3 (C) preblocking with acetazolamide. Tumors are indicated by arrows. Scale bar unit is %ID/g.
Tables
- TABLE 1
Summary of Biologic Evaluation Data of Radiolabeled CA-IX Imaging Probes Shown in Figure 1
Biodistribution Compound Binding affinity Ki (nM) Tumor model Tumor uptake (%ID/g) Tumor-to-blood ratio Tumor-to-muscle ratio Imaging data Reference A NA NA NA NA NA NA 16 B 58 HT-29 0.13 at 0.5 h 0.75 at 0.5 h NA NA 19 C 59 HT-29 0.2–0.1 at 0.5–4 h 0.0 at 0.5–4 h NA NA 18 D 66 HT-29 0.5–0.1 at 0.5–4 h 0.4–0.5 at 0.5–4 h NA NA 18 E NA HT-29 ≤0.1 at 0.5–4 h ≤1.0 at 0.5–4 h NA NA 18 F NA HT-29 ≤0.2 at 0.5–4 h 0.2–1.0 at 0.5–4 h NA NA 18 G 0.9 (R = 3-NO2) NA NA NA NA NA 22 5.4 (R = 4-Ac) NA NA NA NA NA 22 0.3 (R = 2-CN) NA NA NA NA NA 22 H 45 HT-29 0.83 at 1 h <1.0 at 1 h <1.0 at 1 h NA 21 I 124 HT-29, U373 <0.25 at 2–4 h NA NA No tumor visualization 39 J 9.0 NA NA NA NA NA 23 K 9.3 (R = Me) HT-29 0.51 at 1 h ∼1.0 at 1 h ∼1.0 at 1 h No tumor visualization 20 9.6 (R = Ac) HT-29 0.59 at 1 h ∼1.0 at 1 h ∼1.0 at 1 h No tumor visualization 20 9.1 (R = Cl) HT-29 0.98 at 1 h ∼1.0 at 1 h ∼1.0 at 1 h No tumor visualization 20 L 5.2 NA NA NA NA NA 24 M 7.0 NA NA NA NA NA 24 N 70 HT-29 1.16 at 1 h <1.0 at 1 h ∼1.0 at 1 h No tumor visualization 21 NA = not available.
18F-AmBF3-(ABS)3 Organ 18F-AmBF3-AEBS, 1 h after injection 18F-AmBF3-ABS, 1 h after injection 18F-AmBF3-(AEBS)3, 1 h after injection 0.5 h after injection 1 h after injection, unblocked 1 h after injection, blocked* 2 h after injection Blood 0.56 ± 0.05 0.51 ± 0.05 0.19 ± 0.20 0.26 ± 0.02 0.09 ± 0.05 0.17 ± 0.17 0.07 ± 0.01 Fat 0.08 ± 0.03 0.08 ± 0.03 0.04 ± 0.05 0.16 ± 0.08 0.02 ± 0.01 0.03 ± 0.04 0.02 ± 0.00 Testes 0.14 ± 0.05 0.23 ± 0.15 0.04 ± 0.05 0.20 ± 0.11 0.04 ± 0.01 0.03 ± 0.02 0.03 ± 0.00 Stomach 0.54 ± 0.39 2.32 ± 2.14 1.03 ± 0.27 4.66 ± 4.06 1.90 ± 1.62 0.26 ± 0.36 0.44 ± 0.26 Spleen 0.38 ± 0.03 0.54 ± 0.31 0.55 ± 0.73 0.68 ± 0.24 0.37 ± 0.34 0.19 ± 0.24 0.19 ± 0.05 Liver 10.87 ± 0.53 13.64 ± 2.49 0.98 ± 0.67 9.64 ± 3.66 0.97 ± 0.27 0.34 ± 0.18† 0.58 ± 0.19 Pancreas 0.59 ± 0.07 0.57 ± 0.18 0.07 ± 0.05 0.22 ± 0.10 0.07 ± 0.05 0.08 ± 0.11 0.05 ± 0.03 Adrenals 0.32 ± 0.10 0.54 ± 0.27 0.34 ± 0.50 0.97 ± 1.02 0.21 ± 0.15 0.08 ± 0.03 0.26 ± 0.14 Kidney 74.33 ± 19.64 52.70 ± 14.09 0.94 ± 0.32 18.63 ± 3.41 1.78 ± 0.49 0.14 ± 0.04† 5.86 ± 0.86 Lungs 0.90 ± 0.18 1.97 ± 0.11 0.48 ± 0.54 2.75 ± 0.52 0.41 ± 0.29 0.23 ± 0.14 0.24 ± 0.04 Heart 0.29 ± 0.04 0.27 ± 0.02 0.10 ± 0.07 0.32 ± 0.05 0.08 ± 0.04 0.04 ± 0.03 0.08 ± 0.04 Muscle 0.18 ± 0.05 0.32 ± 0.11 0.07 ± 0.03 0.26 ± 0.08 0.04 ± 0.02 0.03 ± 0.01 0.10 ± 0.05 Bone 2.05 ± 0.36 0.85 ± 0.11 0.18 ± 0.12 0.52 ± 0.09 0.21 ± 0.09 0.10 ± 0.04 0.34 ± 0.02 Brain 0.05 ± 0.02 0.04 ± 0.00 0.02 ± 0.02 0.09 ± 0.02 0.02 ± 0.01 0.01 ± 0.01 0.02 ± 0.01 Tumor 0.56 ± 0.11 0.64 ± 0.08 0.30 ± 0.10 0.70 ± 0.13 0.33 ± 0.07 0.06 ± 0.01† 0.24 ± 0.05 Tumor-to-liver 0.05 ± 0.01 0.05 ± 0.01 0.37 ± 0.14 0.07 ± 0.03 0.35 ± 0.07 0.19 ± 0.04† 0.42 ± 0.07 Tumor-to-blood 1.01 ± 0.25 1.24 ± 0.12 2.88 ± 1.81 2.74 ± 0.68 3.93 ± 1.26 1.08 ± 1.03† 3.53 ± 0.55 Tumor-to-muscle 3.18 ± 0.63 2.15 ± 0.66 4.94 ± 2.76 2.87 ± 1.43 9.55 ± 2.96 1.95 ± 0.52† 2.78 ± 1.44
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