Article Figures & Data
Figures
- FIGURE 1.
Percentage of donor chimerism in granulocytes, MNCs, and CD3+ cells in dogs treated with 211At-anti-CD45 mAb conditioning in DLA-haploidentical HCT. Peripheral blood was taken from recipient dogs at serial time points and assessed for donor origin by polymerase chain reaction assay of polymorphic (CA)n dinucleotide repeats after extraction of genomic DNA from cells of interest, to calculate percentage donor chimerism in MNCs (A), granulocytes (B), or CD3+ T cells (C) over time. N.D. = not done.
- FIGURE 2.
Blood count recovery after 211At-CD45-B10 conditioning in DLA-haploidentical HCT. Peripheral blood from recipient dogs was drawn from baseline through HCT and followed up at serial time points to measure granulocytes (A), lymphocytes (B), and platelets (C). N.D. = not done.
- FIGURE 3.
Blood clearance and weekly chimerism by blood’s absorbed dose. (A) Blood samples were obtained at serial time points, and radioactivity measurements were made to estimate absorbed radiation dose (Gy) to blood for injected 211At activity. Animals receiving 0.75 mg/kg dose of mAb are indicated by dashed line, and animals receiving 0.50 mg/kg are indicated by solid line connecting solid circles. (B) Donor MNC chimerism by total absorbed radiation dose delivered to peripheral blood from weeks 1 to 6 after HCT. %ID = percentage injected dose.
- FIGURE 4.
211At distribution in lymph nodes taken from dog H700 at 2 different time points after 211At-CD45-B10 injection, as determined by α-camera imaging and hematoxylin and eosin staining of consecutive cryosections. Radioactivity was heterogeneously localized, predominantly to T-cell–rich regions in cortical follicles.
- FIGURE 5.
Histopathology and immunohistochemistry staining on lymph nodes from dog H700, biopsied 2 and 19 h after 211At-CD45-B10 injection, showing that apoptosis progressed with time. Representative lymph node sections were stained with hematoxylin and eosin (H&E) and immunostained for T cells (CD3), apoptosis (cleaved caspase-3 [CC3]), and macrophages (MAC 387). Scale bar represents 100 μm.
Tables
211At % donor MNC engraftment Dog no. MBq/kg mAb/kg MNC/kg CD34+/kg Max Day 28 Final Survival (d) Cause of death H707 14.06 (0.380) 0.75 12.5 2.9 81 76 65 45 CHV H719 13.653 (0.369) 0.75 19.0 1.0 100 N.D. 82 23 Intussusception, CHV H700 23.199 (0.627) 0.75 10.9 3.9 87 N.D. 87 5 Intussusception H695 8.436 (0.228) 0.5 2.9 0.7 55 49 3 194 PTLD H834 10.767 (0.291) 0.5 6.2 1.7 77 77 72 83 CHV H856 10.767 (0.291) 0.5 4.0 1.1 27 24 6 76 Hemorrhage H762 10.841 (0.293) 0.5 14.5 3.3 94 92 68 126 PTLD H765 11.359 (0.307) 0.5 9.3 2.3 86 67 45 182 PTLD H751 12.876 (0.348) 0.5 10.3 2.7 96 90 95 307 End of study H699 13.949 (0.377) 0.5 13.0 2.5 94 87 91 63 CHV H741 13.986 (0.378) 0.5 8.3 1.0 45 N.D. 45 10 Intussusception/CHV H763 14.282 (0.386) 0.5 4.9 2.4 73 N.D. 73 10 Hemorrhage H714 14.504 (0.392) 0.5 7.3 2.9 71 N.D. 71 23 Intussusception H764 14.615 (0.395) 0.5 4.8 1.2 65 65 42 117 Bronchiolitis H766 14.8 (0.400) 0.5 8.2 1.2 99 96 99 32 Intussusception H502 22.644 (0.612) 0.5 15.9 6.3 72 68 22 132 PTLD H505 22.792 (0.616) 0.5 13.5 1.9 88 83 88 32 Intussusception At = astatine; max = maximum.
Data in parentheses are mCi/kg. Total of 17 dogs received 211At-anti-CD45 mAb. Initial donor engraftment was demonstrated in all subjects, with maximum chimerism ranging between 27% and 100%.
N.D. = not done.
Dog no. mAb dose (mAb/kg) 211At activity MBq (mCi) Absorbed dose to blood (Gy) Radiation dose/injected activity (Gy/MBq) H700 0.75 301 (8.135) 4.30 0.014 H719 0.75 108 (2.919) 2.81 0.026 H707 0.75 136 (3.676) 2.28 0.017 H695 0.5 105 (2.838) 1.17 0.011 H834 0.5 123 (3.324) 1.09 0.009 H856 0.5 107 (2.892) 0.74 0.007 H762 0.5 133 (3.595) 1.68 0.013 H765 0.5 109 (2.946) 1.05 0.010 H751 0.5 122 (3.297) 1.69 0.014 H699 0.5 121 (3.27) 1.89 0.016 H741 0.5 172 (4.649) 1.04 0.006 H763 0.5 156 (4.216) 2.27 0.015 H714 0.5 147 (3.973) 1.58 0.011 H764 0.5 159 (4.297) 1.09 0.007 H766 0.5 184 (4.973) 2.22 0.012 H502* 0.5 226 (6.108) N.D. N.D. H505* 0.5 227 (6.135) N.D. N.D. ↵* Tissues for α-camera imaging and dosimetry were not collected from H502 and H505; thus, absorbed radiation doses were not determined.
N.D. = not done.
Data in parentheses are mCi.
