Article Figures & Data
Figures
- FIGURE 1.
Kaplan–Meier survival curve of control vs. 177Lu-AMBA-treated mice bearing LNCaP or DU145 xenografts. Each radiotherapy study consisted of control group that received vehicle alone and treated group that received 177Lu-AMBA (27.75 MBq). Within each tumor type, there was no significant difference in fractional survival between control and treated groups. Control LNCaP mice vs. treated LNCaP mice: P = 0.529; control DU145 mice vs. treated DU145 mice: P = 0.484 (log-rank test).
- FIGURE 2.
Photographs of LNCaP ecchymosis. (A) Control mouse on study day 22. (B) 177Lu-AMBA–treated mouse on study day 28. (C) LNCaP xenograft shows reduced ecchymosis when compared with control. Mice treated with 177Lu-AMBA (27.75 MBq) had significant reduction in observable ecchymosis (P = 0.0056, log-rank test). Observations were made 3 times per week for duration of study.
- FIGURE 3.
Representative autoradiographs (left) and H&E staining (right) of imaged PC-3 (row A) and LNCaP (row B) xenografts. PC-3 tumor sections were exposed to film for 6 h, LNCaP sections for 24 h.
- FIGURE 4.
Representative histomicrographs of LNCaP from control mice and 177Lu-AMBA-treated mice. Control LNCaP tumors (A) show greater population of amorphous VEGFR-2 (red) immunofluorescent staining vessels than do treated LNCaP tumors (B). Treated tumors show increase of CD31-positive (green) organized vessels. Areas of overlapping VEGFR-2 and CD31 immunoreactivity are present (yellow) in both specimens. (×10)
- FIGURE 5.
Representative histomicrographs show that relative area of blood pooling in LNCaP tumors was higher in control LNCaP tumors (A) than in treated tumors (B). (×40)
Tables
- TABLE 1
In Vitro Internalization and Efflux of Radiolabeled GRP-R Binding Peptide 177Lu-AMBA in DU145, LNCaP, and PC-3 Cells
Cell line Internalized 2 h (% ± SD) Membrane-bound 2 h (% ± SD) Efflux 2 h (% ± SD) DU145 (n = 5) 63.9 ± 6.9 16.4 ± 3.4 14.21 ± 6.9 LNCaP (n = 5) 47.9 ± 5.3 19.6 ± 3.3 31.38 ± 6.9 PC-3 (n = 3) 74.7 ± 15.3 15.3 ± 2.3 2.89 ± 1.8 - TABLE 2
Biodistribution of 177Lu-AMBA (0.185 MBq) in LNCaP, DU145, and PC-3 Tumor–Bearing Mice
1 h after dose 24 h after dose Organ LNCaP (n = 6) DU145 (n = 8) PC-3* (n = 9) LNCaP (n = 6) DU145 n = 8) PC-3* (n = 9) Tumor (%ID/g) 1.52 ± 0.94 0.95 ± 0.23 6.35 ± 2.23 0.83 ± 0.18 0.52 ± 0.22 3.39 ± 0.85 Blood (%ID/g) 0.16 ± 0.08 0.20 ± 0.06 0.46 ± 0.20 0.01 ± 0.01 0.01 ± 0.01 0.03 ± 0.02 Liver (%ID/organ) 0.21 ± 0.09 0.24 ± 0.10 0.25 ± 0.08 0.07 ± 0.03 0.08 ± 0.03 0.21 ± 0.36 Kidneys (%ID/organ) 2.84 ± 0.07 4.21 ± 1.80 2.95 ± 0.79 1.09 ± 0.14 0.92 ± 0.17 0.91 ± 0.25 Pancreas (%ID/organ) 14.65 ± 3.07 17.14 ± 2.54 17.78 ± 4.07 11.86 ± 2.83 12.41 ± 2.05 12.28 ± 3.50 Gastrointestinal (%ID/organ) 15.19 ± 2.62 10.91 ± 1.45 11.22 ± 3.29 7.21 ± 0.48 5.17 ± 0.86 5.77 ± 1.79 Skin (%ID/g) 0.30 ± 0.12 0.46 ± 0.27 0.33 ± 0.13 0.08 ± 0.02 0.07 ± 0.02 0.10 ± 0.02 Muscle (%ID/g) 0.08 ± 0.04 0.10 ± 0.03 0.09 ± 0.02 0.02 ± 0 0.01 ± 0.01 0.03 ± 0.02 Bladder/urine (%ID/organ) 62.00 ± 2.00 44.3 ± 10.38 55.66 ± 7.28 NA NA NA ↵* Data presented are from Lantry et al. (11).
NA = not applicable.
- TABLE 3
Tumor Mean Time to Progression After 177Lu-AMBA Treatment (27.75 MBq) in LNCaP and DU145 Tumor–Bearing Mice, Compared with PC-3 Historic Data
Group Mean time to progression (d) LNCaP control 14 LNCaP + 177Lu-AMBA 28 DU145 control 7 DU145 + 177Lu-AMBA 11 PC-3 control* 19 PC-3 + 177Lu-AMBA* 37 ↵* Data presented are from Lantry et al (11).
- TABLE 4
Modified WHO 2-Dimensional Criteria as Applied to DU145, LNCaP, and PC-3 Radiotherapies
PC-3* (120 d) LNCaP (60 d) DU145 (60 d) Classification Control Treated Control Treated Control Treated Progressive disease 100% 22% 91% 42% 92% 42% Stable disease 0 3% 0 0 0 0 Partial response 0 44% 9% 8% 8% 58% Complete response 0 31% 0 50% 0 0 ↵* Data presented are from Lantry et al. (11).
Cell line Average tumor weight (g) ROI %ID %ID/g PC-3 (n = 5) 0.28 ± 0.07 0.92 ± 0.31 2.70 ± 0.90 LNCaP (n = 3) 0.27 ± 0.09 0.15 ± 0.09 0.26 ± 0.13 DU145 (n = 2) 0.33 ± 0.03 0.16 ± 0.03 0.17 ± 0.04 Mice bearing PC-3, LNCaP, or DU145 tumors received intravenous injection of 177Lu-AMBA (27.75 MBq). After 24-h residence, mice were anesthetized and planar images were acquired. Tumor ROI were analyzed for 177Lu activity. Tumors were then excised, weighed, and counted. ROI = region of interest.
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