title: Long-term in vivo monitoring of mouse and human hematopoietic stem cell engraftment with a human positron emission tomography reporter gene.
abstract: 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 [(18)F]-L-FMAU (1-(2-deoxy-2-(18)fluoro-β-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.
authors: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors: Melissa N
authors: MN
authors: McCracken
authors: Eric H
authors: EH
authors: Gschweng
authors: Evan
authors: E
authors: Nair-Gill
authors: Jami
authors: J
authors: McLaughlin
authors: Aaron R
authors: AR
authors: Cooper
authors: Mireille
authors: M
authors: Riedinger
authors: Donghui
authors: D
authors: Cheng
authors: Christopher
authors: C
authors: Nosala
authors: Donald B
authors: DB
authors: Kohn
authors: Owen N
authors: ON
authors: Witte
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003842:Deoxycytidine Kinase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000000981:diagnostic imaging* / Q000378:metabolism; D007150:Immunohistochemistry; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016513:Mice, SCID; D009154:Mutation; D049268:Positron-Emission Tomography / Q000379:methods*; D013950:Thymus Gland / Q000000981:diagnostic imaging / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D005462:Fluorine Radioisotopes; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D008164:Luminescent Proteins; D001086:Arabinofuranosyluracil; D003842:Deoxycytidine Kinase; C034935:clevudine