Article Figures & Data
Figures
- FIGURE 1.
Increased tissue uptake of 68Ga-DOTA-E[c(RGDfK)]2 in Sharpincpdm mice. (A) Alopecia on dorsal skin of Sharpincpdm mouse, with wt littermate for comparison. (B) Ex vivo uptake of 68Ga-DOTA-E[c(RGDfK)]2 in Sharpincpdm and wt mice without tumors. (C) Competition with nonlabeled DOTA-E[c(RGDfK)]2 peptide and imaging with control peptide 68Ga-DOTA-E[c(RGEfK)]2 revealing specific binding of tracer. Ex vivo results are expressed as percentage of injected radioactivity dose per gram of tissue (%ID/g). n = 4–9/group. *P < 0.05. **P < 0.01. ***P < 0.001.
- FIGURE 2.
SHARPIN deficiency increases metastasis but not growth in tumor microenvironment. (A) Growth curves of B16 melanoma tumors during follow-up period (n = 8–9/group). (B) Tumor volume at end of experiment in wt and Sharpincpdm mice. (C) Pie-chart presenting lymph node metastasis (red) vs. no metastasis (black) in B16 melanoma tumor–bearing wt and Sharpincpdm mice. (D) Quantification of blood flow in B16 melanoma tumors.
- FIGURE 3.
68Ga-DOTA-E[c(RGDfK)]2 binding is enhanced in SHARPIN-deficient tumor microenvironment. (A) Representative autoradiographs (ARG) and corresponding hematoxylin–eosin (HE) staining of B16 melanoma tumors (scale bar, 2 mm). (B) Quantification of autoradiographs showing distribution of 68Ga-DOTA-E[c(RGDfK)]2 radioactivity concentration in tumor, skin, and muscle (n = 12/group). (C) Representative coronal PET/CT images of wt and Sharpincpdm tumor–bearing mice and in vivo tumor uptake of 68Ga-DOTA-E[c(RGDfK)]2 in wt and Sharpincpdm mice. Bars show SUVmean 45–60 min after injection. (D) In vivo tumor uptake of 68Ga-DOTA-Siglec-9 in wt and Sharpincpdm mice. Bars show SUVmean 20–30 min after injection. PSL = photostimulated luminescence.
- FIGURE 4.
Stromal SHARPIN regulates tumor vascularization. (A–C) Representative cryosections of B16 tumors from wt and Sharpincpdm mouse immunolabeled with VAP-1 (A), CD31 (B), and β3 integrin antibody (C). Scale bar, 200 μm. Bars show VAP-1–positive, CD31-positive, and β3 integrin–positive tumor areas from B16 tumors implanted into wt and Sharpincpdm mice.
Tables
- TABLE 1
Ex Vivo Biodistribution of 68Ga-DOTA-E[c(RGDfK)]2 in Tumor-Bearing Mice at Days 9–10 After Inoculation
Site Sharpincpdm wt P Aorta 4.3 ± 0.81 2.1 ± 0.18 <0.05 Brown adipose tissue 0.92 ± 0.15 0.51 ± 0.037 <0.05 Blood 1.5 ± 0.43 0.60 ± 0.058 NS Bone 1.4 ± 0.15 0.87 ± 0.037 <0.05 Heart 0.82 ± 0.14 0.51 ± 0.032 <0.05 Lungs 3.0 ± 0.37 2.0 ± 0.079 <0.05 Lymph nodes 2.0 ± 0.28 0.81 ± 0.056 <0.01 Muscle 0.58 ± 0.079 0.36 ± 0.016 <0.05 Skin 2.9 ± 0.41 1.3 ± 0.070 <0.01 Small intestine 5.5 ± 0.62 3.2 ± 0.39 <0.05 Thymus 1.4 ± 0.21 0.79 ± 0.041 <0.05 Tumor 1.9 ± 0.45 1.0 ± 0.15 <0.05 White adipose tissue 0.68 ± 0.16 0.43 ± 0.11 NS Results are expressed as percentage of injected radioactivity dose per gram of tissue (mean ± SEM).
NS = not statistically significant.
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