MicroSPECT/CT imaging of primary human AML engrafted into the bone marrow and spleen of NOD/SCID mice using In-111-DTPA-NLS-CSL360 radioimmunoconjugates recognizing the CD123(+)/CD131(-) epitope expressed by leukemia stem cells

作者：Leyton Jeffrey V; Williams Brent; Gao Catherine; Keating Armand; Minden Mark; Reilly Raymond M^*

来源：Leukemia Research, 2014, 38(11): 1367-1373.

DOI：10.1016/j.leukres.2014.09.005

• CD123
• MicroSPECT/CT
• Leukemia stem cells
• NOD/SCID mouse
• Radioimmunotherapy

Engraftment of primary human acute myeloid leukemia (AML) specimens into the bone marrow (BM) of NOD/SCID mice has been used to study leukemia biology and new treatments for the disease. CSL360 is a chimeric IgG(1) monoclonal antibody that recognizes CD123 (IL-3 receptor alpha-subchain) expressed in the absence of CD131 (beta-subchain), an epitope that is displayed by leukemia stem cells (LSCs). We are studying CSL360 modified with diethylenetriaminepentaacetic acid (DTPA) for complexing In-111 and 13-mer nuclear translocation sequence (NLS) peptides to enable nuclear importation in LSCs for Auger electron radioimmunotherapy (RIT) of AML. We demonstrate that microSPECT/CT imaging using In-111-DTPA-NLS-CSL360 revealed engraftment of primary human AML specimens into the BM and spleen of NOD/SCID mice. Our results suggest that microSPECT/CT imaging is a powerful tool which enables non-invasive assessment of the engraftment of AML into NOD/SCID mice and in the current study specifically probes an epitope displayed by the LSC subpopulation. The targeting of In-111-DTPA-NLS-CSL360 to sites of AML engraftment in the NOD/SCID mouse model is encouraging for future RIT studies. Ultimately, SPECT imaging could be applied in AML patients to assess the delivery of In-111-DTPA-NLS-CSL360 to sites of leukemia and be combined with Auger electron RIT using the same agent targeting the LSC populationas a "theranostic" pair.

• 出版日期2014-11
• 单位河北医科大学