RT Journal Article
SR Electronic
T1 α-Imaging Confirmed Efficient Targeting of CD45-Positive Cells After <sup>211</sup>At-Radioimmunotherapy for Hematopoietic Cell Transplantation
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1766
OP 1773
DO 10.2967/jnumed.115.162388
VO 56
IS 11
A1 Frost, Sofia H.L.
A1 Miller, Brian W.
A1 Bäck, Tom A.
A1 Santos, Erlinda B.
A1 Hamlin, Donald K.
A1 Knoblaugh, Sue E.
A1 Frayo, Shani L.
A1 Kenoyer, Aimee L.
A1 Storb, Rainer
A1 Press, Oliver W.
A1 Wilbur, D. Scott
A1 Pagel, John M.
A1 Sandmaier, Brenda M.
YR 2015
UL http://jnm.snmjournals.org/content/56/11/1766.abstract
AB 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.