Possibility of Cancer-stem-cell-targeted Radioimmunotherapy for Acute Myelogenous Leukemia Using At-CXCR4 Monoclonal Antibody

Overview

Journal Sci Rep

Specialty Science

Date 2020 Apr 24

PMID 32321944

Citations 11

Authors

Noboru Oriuchi

Miho Aoki

Naoyuki Ukon

Kohshin Washiyama

Chengbo Tan

Saki Shimoyama

Ken-Ichi Nishijima

Kazuhiro Takahashi

Hiroshi Ito

Takayuki Ikezoe

Songji Zhao

Affiliations

Soon will be listed here.

Abstract

To explore stem-cell-targeted radioimmunotherapy with α-particles in acute myelogenous leukemia (AML), pharmacokinetics and dosimetry of the At-labeled anti-C-X-C chemokine receptor type 4 monoclonal antibody (At-CXCR4 mAb) were conducted using tumor xenografted mice. The biological half-life of At-CXCR4 mAb in blood was 15.0 h. The highest tumor uptake of 5.05%ID/g with the highest tumor-to-muscle ratio of 8.51 ± 6.14 was obtained at 6 h. Radiation dosimetry estimated with a human phantom showed absorbed doses of 0.512 mGy/MBq in the bone marrow, 0.287 mGy/MBq in the kidney, and <1 mGy/MBq in other major organs except bone. Sphere model analysis revealed 22.8 mGy/MBq in a tumor of 10 g; in this case, the tumor-to-bone marrow and tumor-to-kidney ratios were 44.5 and 79.4, respectively. The stem-cell-targeted α-particle therapy using At-CXCR4 mAb for AML appears possible and requires further therapeutic studies.

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