Article Figures & Data
Figures
- FIGURE 1.
(A) Schematic illustration of functionalized QD probe for in vivo cancer dual-targeting and dual-modality imaging: structure of multiplex modifying multifunctional QD probe (left), structure of single modifying multifunctional QD probe (middle), and strategy for enhancing synergistic binding of heterodimeric multifunctional QD probe (right). (B) Synthesis of QD-RGD-BBN. (C) Synthesis of dual receptor–targeting dual-modality PET probe 18F-FP-QD-RGD-BBN. CdTe = cadmium telluride; DMSO = dimethyl sulfoxide; TFA = trifluoroacetic acid.
- FIGURE 2.
Characterization of QD probes. (A) Dynamic light scattering data of QD705. (B) Dynamic light scattering data of QD-RGD-BBN. (C) Fluorescence spectra of QD-RGD-BBN and QD705 in aqueous solution. (D) Ultraviolet visible absorbance spectra of NH2-RGD-BBN, QD-RGD-BBN, and QD705.
- FIGURE 3.
In vitro staining of PC-3 cells (both integrin αvβ3 and GRPR high expression) using 1 nM QD-RGD-BBN (left-first column) and 1 nM QD705 (right-first column). Staining of PC-3 cells with 1 nM QD-RGD-BBN in presence of 2 μM BBN (QD-RGD-BBN + BBN Block), 2 μM RGD2 (QD-RGD-BBN + RGD2 Block), and mixture of 2 μM BBN and 2 μM RGD2 (QD-RGD-BBN + RGD-BBN Block) is also shown. Filter set: excitation, 420/40 nm; emission, 705/40 nm. Magnification, ×400, 0.5-s exposure. All fluorescence images were acquired under same condition and displayed under same scale.
- FIGURE 4.
(A) In vivo NIRF imaging of PC-3 tumor–bearing mice at 0.5, 1, 5, 7, and 24 h after injection of 200 pmol QD-RGD-BBN. Arrows indicate tumor. (B) Tumor-to-muscle uptake ratios (Tu/Mu) of mice injected with QD705 and QD-RGD-BBN. Data are mean ± SD. *P < 0.05, as compared with mice injected with QD705, 1-tailed paired Student t test (n = 3). **P < 0.01.
- FIGURE 5.
Ex vivo NIRF imaging. (A) NIRF image of harvested major organs at 5 h after injection of QD-RGD-BBN. (B) NIRF image of harvested major organs at 5 h after injection of QD705. 1 = bone; 2 = brain; 3 = heart; 4 =spleen; 5 = kidney; 6 = liver; 7 = tumor; 8 = muscle; 9 = skin; 10 = intestine; 11 = lung; 12 = stomach.
- FIGURE 6.
PET imaging of PC-3 tumor–bearing mice with targeting dual-receptor PET/NIRF probe. (A) PET images of same mouse at 30, 60, 90, and 120 min after injection of 18F-FP-QD-RGD-BBN and in presence of blocking agent RGD-BBN. Red arrows indicate tumor. (B) Uptake of 18F-FP-QD-RGD-BBN in tumor, muscle, and brain over time, as quantified by ROI analysis of small-animal PET scans (n = 3 per group). (C) Tumor uptake of 18F-FP-QD-RGD-BBN at 60 min after injection in absence of blocking agent (control) and in presence of RGD-BBN, as quantified by ROI analysis of small-animal PET scans (n = 3 per group). %ID/g = percentage injected dose per gram.
Tables
Organ 5 min 30 min 60 min 120 min Blood 4.57 ± 0.96 3.01 ± 0.50 1.81 ± 0.11 1.73 ± 0.17 Brain 1.89 ± 0.33 1.86 ± 0.20 1.17 ± 0.07 1.04 ± 0.13 Heart 2.51 ± 0.44 1.98 ± 0.12 1.39 ± 0.25 1.36 ± 0.30 Lung 6.87 ± 2.56 3.49 ± 0.74 2.22 ± 0.42 1.50 ± 0.36 Liver 7.03 ± 0.69 3.46 ± 0.84 2.19 ± 0.14 1.98 ± 0.38 Spleen 1.83 ± 0.63 1.62 ± 0.33 1.04 ± 0.20 0.81 ± 0.15 Pancreas 2.73 ± 0.77 1.59 ± 0.43 0.88 ± 0.22 0.61 ± 0.14 Kidneys 10.8 ± 3.82 7.35 ± 1.69 2.60 ± 0.44 1.98 ± 0.34 Intestine 2.56 ± 0.63 3.53 ± 0.69 1.94 ± 0.56 1.56 ± 0.28 Muscle 2.20 ± 0.71 1.51 ± 0.38 0.97 ± 0.09 0.69 ± 0.15 Stomach 2.49 ± 0.68 1.61 ± 0.66 0.96 ± 0.24 0.88 ± 0.10 Bone 1.78 ± 0.61 1.72 ± 0.25 1.04 ± 0.24 0.92 ± 0.14 Data are average percentage injected dose per gram, mean ± SD (n = 4).
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