Long-term in vivo monitoring of mouse and human hematopoietic stem cell engraftment with a human positron emission tomography reporter gene

作者：McCracken Melissa N; Gschweng Eric H; Nair Gill Evan; McLaughlin Jami; Cooper Aaron R; Riedinger Mireille; Cheng Donghui; Nosala Christopher; Kohn Donald B; Witte Owen N^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(5): 1857-1862.

DOI：10.1073/pnas.1221840110

• gene therapy
• molecular imaging

Positron emission tomography (PET) reporter genes allow noninvasive whole-body imaging of transplanted cells by detection with radiolabeled probes. We used a human deoxycytidine kinase containing three amino acid substitutions within the active site (hdCK3mut) as a reporter gene in combination with the PET probe [F-18]-L-FMAU (1-(2-deoxy-2-(18)fluoro-beta-L-arabinofuranosyl)-5-methyluracil) to monitor models of mouse and human hematopoietic stem cell (HSC) transplantation. These mutations in hdCK3mut expanded the substrate capacity allowing for reporter-specific detection with a thymidine analog probe. Measurements of long-term engrafted cells (up to 32 wk) demonstrated that hdCK3mut expression is maintained in vivo with no counter selection against reporter-labeled cells. Reporter cells retained equivalent engraftment and differentiation capacity being detected in all major hematopoietic lineages and tissues. This reporter gene and probe should be applicable to noninvasively monitor therapeutic cell transplants in multiple tissues.

• 出版日期2013-1-29