PT  - JOURNAL ARTICLE
AU  - Frost, Sofia H.L.
AU  - Orozco, Johnnie J.
AU  - Bäck, Tom A.
AU  - Miller, Brian W.
AU  - Santos, Erlinda B.
AU  - Kenoyer, Aimee
AU  - Knoblaugh, Sue E.
AU  - Hamlin, Donald K.
AU  - Wilbur, D. Scott
AU  - Sandmaier, Brenda M.
TI  - <sup>211</sup>At-Labeled Anti-CD45 Antibody as a Nonmyeloablative Conditioning for Canine DLA-Haploidentical Stem Cell Transplantation
AID  - 10.2967/jnumed.124.267540
DP  - 2024 Sep 01
TA  - Journal of Nuclear Medicine
PG  - 1443--1449
VI  - 65
IP  - 9
4099  - http://jnm.snmjournals.org/content/65/9/1443.short
4100  - http://jnm.snmjournals.org/content/65/9/1443.full
SO  - J Nucl Med2024 Sep 01; 65
AB  - The α-emitter 211At deposits a high amount of energy within a few cell diameters, resulting in irreparable DNA double-strand breaks while minimizing off-target toxicity. We investigated the use of the 211At-labeled anti-CD45 monoclonal antibody (mAb) 211At-CD45-B10 as a nonmyeloablative conditioning regimen for dog-leukocyte-antigen–haploidentical hematopoietic cell transplantation. Methods: Seventeen healthy dogs were injected with either a 0.50 (n = 14) or 0.75 (n = 3) mg/kg dose of anti-CD45 mAb labeled with 211At (8.436–23.199 MBq [0.228–0.627 mCi/kg]) on day −3. Peripheral blood stem cells from dog-leukocyte-antigen–haploidentical donors were given on day 0. Peripheral blood chimerism was calculated by polymerase chain reaction assays, and blood clearance of the radioimmunoconjugate was studied using enzyme-linked immunosorbent assay and radioactivity measurements of serial blood samples. Results: All dogs achieved donor chimerism by day 28 (range, 27%–100%). The hematopoietic engraftment rate was 100%, though engraftment durability was variable. No difference in absorbed dose to blood was seen for the 2 mAb dosing levels studied. Neutropenia (0–29 cells/μL), lymphocytopenia (36–130 cells/μL), and thrombocytopenia (1.5–9 × 103/μL) with prompt recovery were observed. The main adverse nonhematologic event related to 211At-CD45-B10 was mild reversible transaminitis. Graft-versus-host disease was not seen. Twelve of the 17 dogs survived over 30 d, with donor chimerism ranging from 3% to 99%. Conclusion: The results suggest that nonmyeloablative conditioning with 211At-CD45-B10 could be used in haploidentical hematopoietic cell transplantation though with variable engraftment.