Article Figures & Data
Figures
- FIGURE 1.
Reaction schemes to synthesize precursors and reference standards. (A) One-step synthesis to prepare 4-MBZA is shown. This compound is prepared as reference standard for radiolabeled title compound. (B) Three-step synthesis of precursor 4-HBZA is shown. (C) Radiochemical synthesis of 4-11C-MBZA was accomplished via radiomethylation of 4-HBZA with 11C-methyl-triflate.
- FIGURE 2.
4-11C-MBZA was incubated with 2.5 × 105 B16F1 cells for 1, 15, 30, 45, and 60 min at 37°C. Results are presented as total cell-bound radioactivity (mean ± SD). A 30-min incubation provided significantly higher binding than 15-min incubation (P < 0.05). Binding increased slightly by 60 min, but differences are statistically insignificant (P > 0.1).
- FIGURE 3.
Binding of 4-11C-MBZA to B16F1 melanoma cells, MDA-MB-321, and MCF-10A (2.5 × 105 cells/well). A preferential binding of 4-11C-MBZA to B16F1 melanoma cells is noted. Pretreatment with excess 4-MBZA to block binding sites resulted in 10-fold reduction in binding to melanoma cells and approximately 4-fold reduction for MCF-10A cells. Binding was low for MDA-MB-231 cells and remained unchanged.
- FIGURE 4.
Cell-bound and internalized fraction of 4-11C-MBZA in B16F1 melanoma cells is shown. Overall binding increased proportionally with increased number of cells per well. Nonetheless, internalized fraction remained approximately 55%–60% of total cell associated radioactivity, irrespective of number of cells per well.
- FIGURE 5.
Tumor–to–normal tissue ratio at 10, 20, 45, and 60 min after injection of 4-11C-MBZA using mice bearing B16F1 melanoma tumor xenografts. For most tissues, these ratios increased significantly with time.
- FIGURE 6.
Small-animal PET images of mice bearing B16F1 melanoma tumor xenografts after injection of 4-11C-MBZA. Coronal (top) and axial (bottom) views are summed images showing average uptake in scans from 0 to 5 min (A), 5 to 15 min (B), 15 to 25 min (C), 25 to 35 min (D), and 35 to 45 min (E). Tumor is clearly visible on 5-min images (A) and continued to increase in intensity with time (B–E).
- FIGURE 7.
Time–activity curves generated from small-animal PET images of mouse bearing B16F1 melanoma tumors and injected with 4-11C-MBZA. A high uptake was noted in tumor. Accumulation in most normal tissues was low, and it continued to decrease with time.
Tables
Temperature (°C) NaOH (concentration) NaOH (μL) Yield (%) 20 0.5 M 100 1 60 0.5 M 100 7 60 2 M 100 11 60 4 M 20 25 40 6 M 20 21 60 6 M 20 37 80 6 M 20 51 100 6 M 20 40 - TABLE 2
Biodistribution of 4-11C-MBZA in C57BL Mice Bearing B16F1 Melanoma Tumor Xenografts
%ID/g Organ 10 Min* 20 Min* 30 Min* 45 Min† 60 Min† Liver 6.40 ± 1.46 5.69 ± 0.92 5.62 ± 1.01 5.43 ± 0.84 4.77 ± 1.49 Spleen 4.52 ± 0.39 2.59 ± 0.25 2.22 ± 0.30 1.59 ± 0.34 1.37 ± 0.34 Lung 2.30 ± 0.42 1.23 ± 0.63 0.89 ± 0.23 0.79 ± 0.19 0.81 ± 0.38 Heart 2.36 ± 0.30 1.25 ± 0.23 1.12 ± 0.30 1.02 ± 0.25 0.83 ± 0.23 Kidneys 7.47 ± 1.66 4.26 ± 1.12 3.47 ± 0.42 3.11 ± 1.21 3.09 ± 1.22 Small intestine 2.86 ± 0.43 2.15 ± 0.29 1.97 ± 0.28 1.89 ± 0.59 2.65 ± 1.14 Pancreas 6.48 ± 0.38 3.48 ± 0.61 3.52 ± 0.39 3.49 ± 1.35 4.62 ± 1.88 Bone 2.68 ± 0.90 1.33 ± 0.13 1.04 ± 0.06 0.83 ± 0.19 0.80 ± 0.29 Brain 2.46 ± 0.32 1.66 ± 0.28 1.28 ± 0.25 1.25 ± 0.38 1.08 ± 0.38 Adrenals 1.50 ± 0.23 0.83 ± 0.41 0.66 ± 0.41 0.59 ± 0.32 0.54 ± 0.24 Blood 1.43 ± 0.29 0.89 ± 0.32 1.06 ± 0.12 1.11 ± 0.29 0.95 ± 0.25 Tumor 5.85 ± 0.79 6.13 ± 0.21 6.20 ± 0.83 6.86 ± 1.32 8.13 ± 1.43
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