α-Imaging Confirmed Efficient Targeting of CD45-Positive Cells After 211At-Radioimmunotherapy for Hematopoietic Cell Transplantation

Journal of Nuclear Medicine

Shani L. Frayo¹  Oliver W. Press¹  Brenda M. Sandmaier¹  Sue E. Knoblaugh¹  John M. Pagel¹  Donald K. Hamlin¹  Rainer Storb¹  Aimee L. Kenoyer¹  Brian W. Miller¹  Sofia H.L. Frost¹  Tom A. Bäck¹  Erlinda B. Santos¹  D. Scott Wilbur¹ 

关键词: radioimmunotherapy;    ²¹¹At;    alpha imaging;    CD45;    lymphoma;   

DOI  :  10.2967/jnumed.115.162388

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

α-radioimmunotherapy targeting CD45 may substitute for total-body irradiation in hematopoietic cell transplantation (HCT) preparative regimens for lymphoma. Our goal was to optimize the anti-CD45 monoclonal antibody (mAb; CA12.10C12) protein dose for 211At-radioimmunotherapy, extending the analysis to include intraorgan 211At activity distribution and α-imaging–based small-scale dosimetry, along with immunohistochemical staining. Methods: Eight normal dogs were injected with either a 0.75 (n = 5) or 1.00 (n = 3) mg/kg dose of 211At-B10-CA12.10C12 (11.5–27.6 MBq/kg). Two were euthanized and necropsied 19–22 h after injection, and 6 received autologous HCT 3 d after 211At-radioimmunotherapy, after lymph node and bone marrow biopsies at 2–4 and/or 19 h after injection. Blood was sampled to study toxicity and clearance; CD45 targeting was evaluated by flow cytometry. 211At localization and small-scale dosimetry were assessed using two α-imaging systems: an α-camera and an ionizing-radiation quantum imaging detector (iQID) camera. Results: 211At uptake was highest in the spleen (0.31–0.61% injected activity [%IA]/g), lymph nodes (0.02–0.16 %IA/g), liver (0.11–0.12 %IA/g), and marrow (0.06–0.08 %IA/g). Lymphocytes in blood and marrow were efficiently targeted using either mAb dose. Lymph nodes remained unsaturated but displayed targeted 211At localization in T lymphocyte–rich areas. Absorbed doses to blood, marrow, and lymph nodes were estimated at 3.1, 2.4, and 3.4 Gy/166 MBq, respectively. All transplanted dogs experienced transient hepatic toxicity. Liver enzyme levels were temporarily elevated in 5 of 6 dogs; one treated with 1.00 mg mAb/kg developed ascites and was euthanized 136 d after HCT. Conclusion: 211At-anti-CD45 radioimmunotherapy with 0.75 mg mAb/kg efficiently targeted blood and marrow without severe toxicity. Dosimetry calculations and observed radiation-induced effects indicated that sufficient 211At-B10-CA12.10C12 localization was achieved for efficient conditioning for HCT.

【 授权许可】

Unknown