Literature DB >> 32169919

Biokinetics of Radiolabeled Monoclonal Antibody BC8: Differences in Biodistribution and Dosimetry Among Hematologic Malignancies.

Manuela Matesan1, Darrell R Fisher2,3, Roger Wong2, Ajay K Gopal4,5, Damian J Green4,5, Brenda M Sandmaier4,5, William Bensinger6, John M Pagel6, Johnnie Orozco4,5, Oliver W Press4,5, Ryan D Cassaday4,5, Eric Hutchinson2, Michelle Wanner2, Sujit Pal2, Carolyn Thostenson2, Joseph G Rajendran2.   

Abstract

We reviewed 111In-DOTA-anti-CD45 antibody (BC8) imaging and bone marrow biopsy measurements to ascertain the biodistribution and biokinetics of the radiolabeled antibody and to investigate differences based on type of hematologic malignancy.
Methods: Serial whole-body scintigraphic images (4 time points) were obtained after infusion of the 111In-DOTA-BC8 (176-406 MBq) into 52 adult patients with hematologic malignancies (lymphoma, multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome). Counts were obtained for the regions of interest for spleen, liver, kidneys, testicles (in men), and 2 marrow sites (acetabulum and sacrum), and correction for attenuation and background was made. Bone marrow biopsies were obtained 14-24 h after infusion, and the percentage of administered activity was determined. Absorbed radiation doses were calculated.
Results: Initial uptake in liver averaged 32% ± 8.4% (SD) of administered activity (52 patients), which cleared monoexponentially with a biologic half-time of 293 ± 157 h (33 patients) or did not clear (19 patients). Initial uptake in spleen averaged 22% ± 12% and cleared with a biologic half-time of 271 ± 185 h (36 patients) or longer (6 patients). Initial uptake in kidney averaged 2.4% ± 2.0% and cleared with a biologic half-time of 243 ± 144 h (27 patients) or longer (9 patients). Initial uptake in red marrow averaged 23% ± 11% and cleared with a biologic half-time of 215 ± 107 h (43 patients) or longer (5 patients). Whole-body retention half-time averaged 198 ± 75 h. Splenic uptake was higher in the AML/MDS group than in the lymphoma group (P ≤ 0.05) or the multiple myeloma group (P ≤ 0.10). Liver represented the dose-limiting organ. For liver uptake, no significant differences were observed among the 3 malignancy groups. Average calculated radiation absorbed doses per unit of administered activity for a therapy infusion of 90Y-DOTA-BC8 were 0.35 ± 0.20 cGy/MBq for red marrow, 0.80 ± 0.24 cGy/MBq for liver, 3.0 ± 1.4 cGy/MBq for spleen, 0.055 ± 0.014 cGy/MBq for total body, 0.21 ± 0.15 cGy/MBq for osteogenic cells, and 0.17 ± 0.15 cGy/MBq for kidneys.
Conclusion: 111In-DOTA-BC8 had a long retention time in liver, spleen, kidneys, and red marrow, and the highest absorbed doses were in spleen and liver. Few differences were observed by malignancy type. The exception was greater splenic uptake in the leukemia/MDS group than in the lymphoma or multiple myeloma group.
© 2020 by the Society of Nuclear Medicine and Molecular Imaging.

Entities:  

Keywords:  BC8; anti-CD45; dosimetry; radioimmunotherapy

Year:  2020        PMID: 32169919      PMCID: PMC7456175          DOI: 10.2967/jnumed.119.234443

Source DB:  PubMed          Journal:  J Nucl Med        ISSN: 0161-5505            Impact factor:   10.057


  21 in total

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