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

作者：Frost Sofia H L^*; Miller Brian W; Baeck Tom A; Santos Erlinda B; Hamlin Donald K; Knoblaugh Sue E; Frayo Shani L; Kenoyer Aimee L; Storb Rainer; Press Oliver W; Wilbur D Scott; Pagel John M; Sandmaier Brenda M

来源：Journal of Nuclear Medicine, 2015, 56(11): 1766-1773.

DOI：10.2967/jnumed.115.162388

• radioimmunotherapy
• At-211
• alpha imaging
• CD45
• lymphoma

alpha-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 At-211-radioimmunotherapy, extending the analysis to include intraorgan At-211 activity distribution and alpha-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 At-211-B10-CA12.10C12 (11.5-27.6 MBq/kg). Two were euthanized and necropsied 19-22 h after injection, and 6 received autologous HOT 3 d after At-211-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. At-211 localization and small-scale dosimetry were assessed using two alpha-imaging systems: an a-camera and an ionizing-radiation quantum imaging detector (iQID) camera. Results: At-211 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 At-211 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 HOT. Conclusion: At-211-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 At-211-B10-CA12.10012 localization was achieved for efficient conditioning for HOT.

• 出版日期2015-11