Article Figures & Data
Figures
- FIGURE 1.
Schematic structure of DOTA-E{E[c(RGDfK)]2}2. The tetrameric RGD peptide was synthesized by coupling Boc-Glu(OSu)-OSu with dimeric RGD peptide E[c(RGDfK)]2 followed by removal of Boc protecting group. DOTA conjugation was realized by reacting monoactive ester of DOTA with the free amino group on the N-terminal glutamate.
- FIGURE 2.
In vitro inhibition of 125I-echistatin binding to αv integrin on human glioblastoma cell line U87MG by echistatin, E[c(EGDfK)]2, DOTA-E[c(EGDfK)]2, E{E[c(RGDfK)]2}2, and DOTA- E{E[c(RGDfK)]2}2. Results are means of 3 experiments.
- FIGURE 3.
(A) Extraction efficiency of liver and kidney homogenates, blood, and urine samples at 30 min, 1 h, and 2 h after tracer injection in normal athymic nude mice (n = 3). (B) Time course of intact tracer in soluble fraction of blood, urine, and organ homogenates. (C) Representative HPLC elution profiles of soluble fraction of blood and urine samples, liver, and kidney homogenates collected 1 h after tracer injection.
- FIGURE 4.
(A) Biodistribution data for 64Cu-DOTA-E{E[c(RGDfK)]2}2 in athymic nude mice bearing subcutaneously xeno-transplanted U87MG tumors. Data are expressed as normalized accumulation of activity in %ID/g ± SD (n = 3). (B) Biodistributions of 64Cu-DOTA-E{E[c(RGDfK)]2}2 in U87MG tumor-bearing athymic nude mice at 1 h with and without coinjection of 10 mg/kg of c(RGDyK) as a blocking agent (n = 3).
- FIGURE 5.
Comparison of biodistributions of 64Cu-DOTA-E{E[c(RGDfK)]2}2 (•) and 64Cu-DOTA-E[c(RGDfK)]2 (○) in U87MG tumor-bearing athymic nude mice. Error bars denote SDs (n = 3).
- FIGURE 6.
(A) Decay-corrected whole-body coronal microPET images of nude mouse bearing human U87MG tumor at 15 and 30 min and at 1, 2, 4, and 18 h (10-min static image) after injection of 9.1 MBq (245 μCi) of 64Cu-DOTA-E{E[c(RGDfK)]2}2. (B) Time–activity curves derived from multiple time-point microPET study. ROIs are shown as the mean %ID/g ± SD (n = 4). (C) Comparison of tumor uptakes in mice injected with 64Cu-DOTA-E{E[c(RGDfK)]2}2 at a dose of 9.3 MBq with (top) or without (bottom) 10 mg/kg c(RGDyK).
Tables
- TABLE 1
Average Fractional Uptake at Time Zero and Biologic Half-Times for Each Organ of Tumor-Bearing Mice According to Biodistribution Data (n = 3)
Organ Fractional uptake (%) Biologic half-times (h) Heart 0.19 3.52 Lung 0.76 3.11 Liver 3.48 10.45 Kidneys 2.49 2.95 Spleen 0.19 6.00 Pancreas 0.09 9.32 Brain 0.05 8.52 Urine*† 25.0 0.05; 1.85 Remainder of body* 9.2 0.07; 4.40 - TABLE 2
Estimated Radiation-Absorbed Doses to Adult Human After Intravenous Injection of 64Cu-DOTA-E{E[c(RGDfK)]2}2 Based on Average Biodistribution Data Obtained in U87MG Glioblastoma-Bearing Nude Mice (n = 3)
Target organ mGy/MBq (SD) rad/mCi (SD) Adrenals 2.07E−03 (3.31E−04) 7.67E−03 (1.23E−03) Brain 4.73E−04 (3.64E−05) 1.75E−03 (1.35E−04) Breasts 6.58E−04 (1.05E−04) 2.43E−03 (3.89E−04) Gallbladder wall 3.00E−03 (4.80E−04) 1.11E−02 (1.78E−03) Lower large intestine 3.94E−03 (6.30E−04) 1.46E−02 (2.34E−03) Small intestine 2.19E−03 (3.50E−04) 8.10E−03 (1.30E−03) Stomach wall 1.28E−03 (2.05E−04) 4.74E−03 (7.58E−04) Upper large intestine 2.04E−03 (3.26E−04) 7.53E−03 (1.20E−03) Heart wall 3.22E−03 (6.15E−05) 1.19E−02 (2.27E−04) Kidneys 2.96E−02 (1.84E−03) 1.10E−01 (6.84E−03) Liver 2.43E−02 (1.56E−03) 8.98E−02 (5.76E−03) Lungs 9.57E−04 (2.34E−05) 3.54E−03 (8.66E−05) Muscle 1.55E−03 (8.90E−05) 5.74E−03 (3.30E−04) Ovaries 3.74E−03 (5.98E−04) 1.38E−02 (2.21E−03) Pancreas 1.15E−02 (4.73E−04) 4.24E−02 (1.74E−03) Red marrow 1.28E−03 (2.05E−04) 4.75E−03 (7.60E−04) Osteogenic cells 1.46E−03 (2.34E−04) 5.41E−03 (8.66E−04) Skin 8.32E−04 (1.33E−04) 3.08E−03 (4.93E−04) Spleen 8.16E−03 (1.64E−03) 3.02E−02 (6.07E−03) Testes 2.72E−03 (4.35E−04) 1.01E−02 (1.62E−03) Thymus 6.80E−04 (1.09E−04) 2.51E−03 (4.02E−04) Thyroid 5.05E−04 (8.08E−05) 1.87E−03 (2.99E−04) Urinary bladder wall 2.62E−01 (4.72E−02) 9.69E−01 (1.75E−01) Uterus 7.92E−03 (1.27E−03) 2.93E−02 (4.69E−03) Total body dose 2.35E−03 (3.76E−04) 8.69E−03 (1.39E−03) Effective dose* 1.64E−02 (2.95E−03) 6.06E−02 (1.09E−02) ↵* In unit of mSv/MBq or rem/mCi.
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