Article Figures & Data
Figures
- FIGURE 1.
PET/CT imaging of NSG mice with established pediatric solid tumor xenografts (arrows) after intravenous injection of 9.2 ± 0.7 MBq of CLR 124. Maximum-intensity projections of representative mice in each cohort are shown at 5 time points after injection.
- FIGURE 2.
Pharmacokinetic profiles of CLR 124 uptake in liver, kidneys, lungs, heart, brain, and bone marrow after intravenous injection. Mean uptake is shown at each time point (n = 15) with error bars for SE.
- FIGURE 3.
Tumor uptake in murine xenograft models of Rh30, TC71, CHLA20 (n = 4), and NB1691 (n = 3) is shown as mean %ID/g with error bars for SE.
- FIGURE 4.
Dose–response relations for mice with Rh30, TC71, CHLA20, and NB1691 xenografts and treated with single dose of CLR 131 MRT. Integral absorbed doses (x-axis) were calculated after 3 half-lives (24 d) after injection for each subject. Tumor growth response is expressed on vertical axis as mean specific growth delay for Rh30, TC71, CHLA20, and NB1691 (n = 7, 7, 6, and 9, respectively) with error bars for SE.
- FIGURE 5.
Whole-body PET/CT imaging and quantitative analysis of tumor-specific uptake of CLR 124 and 124I-MIBG in murine xenograft models of NB1691-hNET. (A) Representative murine xenograft models of NB1691-hNET administered CLR 124 or 124I-MIBG are presented as 3-dimensional renderings of PET (purple and yellow) fused with CT (grayscale) images acquired during peak tumor-specific uptake at 72 and 24 h after injection, respectively. Location of flank tumor is indicated by arrows. (B) PET/CT ROI analysis of tumor and contralateral muscle uptake is shown with mean values (n = 4) and error bars for SE.
Tables
- TABLE 1
Estimated Absorbed Radiation Doses to Organs from Intravenous Administration of CLR 131 in Pediatric and Adult Humans
Organ Child (n = 14; mSv/MBq) Adult (n = 14; mSv/MBq) Adrenals 1.425 ± 0.125 0.446 ± 0.041 Brain 0.969 ± 0.058 0.278 ± 0.017 Breasts 1.103 ± 0.094 0.335 ± 0.029 Gallbladder wall 1.444 ± 0.131 0.471 ± 0.045 Lower large intestine wall 1.346 ± 0.111 0.426 ± 0.036 Small intestine 1.420 ± 0.119 0.438 ± 0.038 Stomach wall 1.346 ± 0.115 0.420 ± 0.037 Upper large intestine wall 1.409 ± 0.119 0.434 ± 0.038 Heart wall 2.673 ± 0.283 0.790 ± 0.085 Kidneys 2.278 ± 0.320 0.669 ± 0.092 Liver 2.516 ± 0.384 0.750 ± 0.114 Lungs 1.888 ± 0.238 0.559 ± 0.070 Muscle 1.219 ± 0.101 0.373 ± 0.032 Ovaries 1.404 ± 0.117 0.438 ± 0.037 Pancreas 1.471 ± 0.130 0.457 ± 0.041 Red marrow 1.825 ± 0.145 0.496 ± 0.041 Osteogenic cells 2.506 ± 0.199 0.840 ± 0.070 Skin 1.053 ± 0.088 0.314 ± 0.027 Spleen 1.346 ± 0.115 0.410 ± 0.036 Testes 1.184 ± 0.098 0.367 ± 0.031 Thymus 1.294 ± 0.108 0.404 ± 0.036 Thyroid 1.326 ± 0.109 0.384 ± 0.033 Urinary bladder wall 1.330 ± 0.110 0.420 ± 0.036 Uterus 1.417 ± 0.118 0.441 ± 0.038 Total body 1.376 ± 0.119 0.406 ± 0.036 Organ dosimetry shows absorbed radiation doses based on CLR 124 uptake data from 14 tumor-bearing mice extrapolated to 5-y-old and adult human models.
- TABLE 2
Subject-Specific Tumor Dosimetry in Murine Xenograft Models of Rh30, TC71, CHLA20, and NB1691 for CLR 131 MRT
Integral prescription dose (Gy/MBq) Xenograft 8 d 24 d ∞ CLR 131 (MBq) to deliver 20 Gy Rh30 0.98 ± 0.19 1.81 ± 0.37 2.08 ± 0.43 9.59 ± 1.98 TC71 0.57 ± 0.11 0.94 ± 0.16 1.06 ± 0.18 18.92 ± 3.18 CHLA20 0.47 ± 0.16 0.81 ± 0.32 0.92 ± 0.37 21.68 ± 8.72 NB1691 0.64 ± 0.10 1.10 ± 0.16 1.26 ± 0.18 15.92 ± 2.29 Integral prescription dose to tumor is shown calculated out to 1 and 3 times half-life of 131I, as well as committed dose integrated out to infinity.
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