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Personalized Medicine and Imaging

Bone Marrow Cell Trafficking Analyzed by 89Zr-oxine Positron Emission Tomography in a Murine Transplantation Model

Kingsley O. Asiedu, Sho Koyasu, Lawrence P. Szajek, Peter L. Choyke and Noriko Sato
Kingsley O. Asiedu
Molecular Imaging Program, NCI, NIH, Bethesda, Maryland.
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Sho Koyasu
Molecular Imaging Program, NCI, NIH, Bethesda, Maryland.
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Lawrence P. Szajek
Positron Emission Tomography Department, Warren Grant Magnuson Clinical Center, NIH, Bethesda, Maryland.
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Peter L. Choyke
Molecular Imaging Program, NCI, NIH, Bethesda, Maryland.
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Noriko Sato
Molecular Imaging Program, NCI, NIH, Bethesda, Maryland.
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  • For correspondence: saton@mail.nih.gov
DOI: 10.1158/1078-0432.CCR-16-1561 Published June 2017
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Abstract

Purpose: The success of hematopoietic stem cell transplantation (HSCT) depends on donor cell homing to the bone marrow. However, there is no reliable method of noninvasively monitoring the kinetics and distribution of transferred cells. Using zirconium-89 (89Zr)-oxine cell labeling combined with PET imaging, we sought to visualize and quantify donor cell homing in a mouse bone marrow transplantation model.

Experimental Design: The effect of 89Zr-oxine labeling on bone marrow cell viability and differentiation was evaluated in vitro. 89Zr-labeled bone marrow cells (2 × 107 cells, 16.6 kBq/106 cells) were transferred intravenously, and serial microPET images were obtained (n = 5). The effect of a CXCR4 inhibitor, plerixafor (5 mg/kg) and G-CSF (2.5 μg) on bone marrow homing and mobilization were examined (n = 4). Engraftment of the transferred 89Zr-labeled cells was evaluated (n = 3).

Results: 89Zr-oxine–labeled bone marrow cells showed delayed proliferation, but differentiated normally. Transferred bone marrow cells rapidly migrated to the bone marrow, spleen, and liver (n = 5). Approximately 36% of donor cells homed to the bone marrow within 4 hours, irrespective of prior bone marrow ablation. Inhibition of CXCR4 by plerixafor alone or with G-CSF significantly blocked the bone marrow homing (P < 0.0001, vs. nontreated, at 2 hours), confirming a crucial role of the CXCR4–CXCL12 system. Mobilization of approximately 0.64% of pretransplanted bone marrow cells induced a 3.8-fold increase of circulating bone marrow cells. 89Zr-labeled donor cells engrafted as well as nonlabeled cells.

Conclusions: 89Zr-oxine PET imaging reveals rapid bone marrow homing of transferred bone marrow cells without impairment of their stem cell functions, and thus, could provide useful information for optimizing HSCT. Clin Cancer Res; 23(11); 2759–68. ©2016 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

  • Received June 21, 2016.
  • Revision received November 29, 2016.
  • Accepted December 8, 2016.
  • ©2016 American Association for Cancer Research.
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Clinical Cancer Research: 23 (11)
June 2017
Volume 23, Issue 11
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Bone Marrow Cell Trafficking Analyzed by 89Zr-oxine Positron Emission Tomography in a Murine Transplantation Model
Kingsley O. Asiedu, Sho Koyasu, Lawrence P. Szajek, Peter L. Choyke and Noriko Sato
Clin Cancer Res June 1 2017 (23) (11) 2759-2768; DOI: 10.1158/1078-0432.CCR-16-1561

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Bone Marrow Cell Trafficking Analyzed by 89Zr-oxine Positron Emission Tomography in a Murine Transplantation Model
Kingsley O. Asiedu, Sho Koyasu, Lawrence P. Szajek, Peter L. Choyke and Noriko Sato
Clin Cancer Res June 1 2017 (23) (11) 2759-2768; DOI: 10.1158/1078-0432.CCR-16-1561
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Clinical Cancer Research
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