RT Journal Article
SR Electronic
T1 <sup>211</sup>At-Labeled Anti-CD45 Antibody as a Nonmyeloablative Conditioning for Canine DLA-Haploidentical Stem Cell Transplantation
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1443
OP 1449
DO 10.2967/jnumed.124.267540
VO 65
IS 9
A1 Frost, Sofia H.L.
A1 Orozco, Johnnie J.
A1 Bäck, Tom A.
A1 Miller, Brian W.
A1 Santos, Erlinda B.
A1 Kenoyer, Aimee
A1 Knoblaugh, Sue E.
A1 Hamlin, Donald K.
A1 Wilbur, D. Scott
A1 Sandmaier, Brenda M.
YR 2024
UL http://jnm.snmjournals.org/content/65/9/1443.abstract
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.